cssi/SciSciGPT-SciSciNet huggingface dataset:
Electroencephalographic analysis of a conditioned reflex to time.

1. During CRT formation fast spindle-like electrical activity with a frequency of 28–32 waves/sec is generated in the cortical projection (auditory, visual) and association (parietal) areas, and it is enhanced in the anterior zones of the brain (somatosensory and motor cortex). 2. During the formation of a reflex to time close interconnection is observed (with respect to spatial synchronous activity of the spindle rhythm with a frequency of 28–32 waves/sec) between cortical projection and integrative-triggering regions, accompanied by periodic “connection” of the parietal association region. 3. The end of the test interval is preceded by short EEG desynchronization, reflecting the beginning of performance of the instrumental reflex. 4. During the formation of a reflex to time correlation is observed between the appearance of spindle-like activity at 28–32 waves/sec on the EEG of the motor cortex and the motor act. 5. In the organization of the CRT as a complex response (actual, trace, and rhythmic processes) different brain systems play unequal roles in the formation of its stages. Sensory systems are responsible primarily for the combination of trace processes on which the formation of the response to time is based. Association structures are mainly involved in afferent synthesis necessary for the current moment of time. Integrative-triggering formations, on the other hand, time the newly formed response to take place at a strictly fixed moment, which depends on the nature of afferentation from the other cerebral systems involved in rhythmic cycles.
Creation of a novel algorithm to identify patients with Becker and Duchenne muscular dystrophy within an administrative database and application of the algorithm to assess cardiovascular morbidity.

BACKGROUND Outcome analyses in large administrative databases are ideal for rare diseases such as Becker and Duchenne muscular dystrophy. Unfortunately, Becker and Duchenne do not yet have specific International Classification of Disease-9/-10 codes. We hypothesised that an algorithm could accurately identify these patients within administrative data and improve assessment of cardiovascular morbidity. METHODS Hospital discharges (n=13,189) for patients with muscular dystrophy classified by International Classification of Disease-9 code: 359.1 were identified from the Pediatric Health Information System database. An identification algorithm was created and then validated at three institutions. Multi-variable generalised linear mixed-effects models were used to estimate the associations of length of stay, hospitalisation cost, and 14-day readmission with age, encounter severity, and respiratory disease accounting for clustering within the hospital. RESULTS The identification algorithm improved identification of patients with Becker and Duchenne from 55% (code 359.1 alone) to 77%. On bi-variate analysis, left ventricular dysfunction and arrhythmia were associated with increased cost of hospitalisation, length of stay, and mortality (p<0.001). After adjustment, Becker and Duchenne patients with left ventricular dysfunction and arrhythmia had increased length of stay with rate ratio 1.4 and 1.2 (p<0.001 and p=0.004) and increased cost of hospitalization with rate ratio 1.4 and 1.4 (both p<0.001). CONCLUSIONS Our algorithm accurately identifies patients with Becker and Duchenne and can be used for future analysis of administrative data. Our analysis demonstrates the significant effects of cardiovascular disease on length of stay and hospitalisation cost in patients with Becker and Duchenne. Better recognition of the contribution of cardiovascular disease during hospitalisation with earlier more intensive evaluation and therapy may help improve outcomes in this patient population.
Limits of tax regulation: Evidence from strategic R&D classification and the R&D tax credit

Abstract We investigate a tax avoidance strategy where firms use the ambiguity inherent in tax reporting to classify indirect costs as research and development (R&D) expenditures to take advantage of the R&D tax credit. We label this tax practice “strategic R&D classification”. We find a one standard deviation increase in strategic R&D classification leads, on average, to a 1.7% (1.5%) reduction in GAAP (cash) effective tax rates, suggesting this practice provides significant tax savings. However, we also find strategic R&D classification is related to both the level and changes in uncertain tax benefit liabilities required to be recognized under FIN 48, suggesting this practice comes with financial reporting costs. Our study contributes to the literature by documenting some of the costs and benefits associated with a previously unexplored tax strategy, and highlights the limitations faced by tax authorities in monitoring firms’ R&D tax credit.
NATF (Native and Tissue-Specific Fluorescence): A Strategy for Bright, Tissue-Specific GFP Labeling of Native Proteins in Caenorhabditis elegans.

GFP labeling by genome editing can reveal the authentic location of a native protein, but is frequently hampered by weak GFP signals and broad expression across a range of tissues that may obscure cell-specific localization. To overcome these problems, we engineered a Native And Tissue-specific Fluorescence (NATF) strategy that combines genome editing and split-GFP to yield bright, cell-specific protein labeling. We use clustered regularly interspaced short palindromic repeats CRISPR/Cas9 to insert a tandem array of seven copies of the GFP11 β-strand (gfp11x7 ) at the genomic locus of each target protein. The resultant gfp11x7 knock-in strain is then crossed with separate reporter lines that express the complementing split-GFP fragment (gfp1-10) in specific cell types, thus affording tissue-specific labeling of the target protein at its native level. We show that NATF reveals the otherwise undetectable intracellular location of the immunoglobulin protein OIG-1 and demarcates the receptor auxiliary protein LEV-10 at cell-specific synaptic domains in the Caenorhabditis elegans nervous system.
Firm value in commonly uncertain times: the divergent effects of corporate governance and CSR

Economic uncertainty disrupts firms’ ability to create value. Most related literature examines how various organizational characteristics affect value under extreme conditions – the global financia...
Error Costs, Ratio Tests, and Patent Antitrust Law

This paper examines the welfare tradeoff between patent and antitrust law. Since patent and antitrust law have contradictory goals, the question that naturally arises is how one should choose between the two in instances where there is a conflict. One sensible approach to choosing between two legal standards—or between proof standards with respect to evidence—is to consider the relative costs of errors. The approach in this paper is to consider the ratio of false positives to false negatives in patent antitrust. We find that the relevant error-cost ratio for patent antitrust is the proportion of the sum of the monopoly profit and the residual consumer surplus to the deadweight loss. This error-cost ratio—for a wide range of deterministic demand functions—ranges from infinity to a low of roughly three. This suggests that patent antitrust law should err on the side of protecting innovation incentives.
PENGARUH KREDIT USAHA KECIL (KUK) TERHADAP PERKEMBANGAN PRODUKSI DAN TENAGA KERJA PADA USAHA KECIL DI SUMATERA BARAT.

Penelitian ini bertujuan untuk menganalisis : (1) Pengaruh Kredit Usaha Kecil (KUK) terhadap jumlah produksi usaha kecil di Sumatera Barat. (2) Pengaruh Kredit Usaha Kecil (KUK) terhadap jumlah tenaga kerja di Sumatera Barat. Jenis penelitian ini adalah penelitian deskriptif dan asosiatif yaitu penelitian yang mendeskripsikan variabel penelitian dan menemukan ada tidaknya pengaruh antara variabel bebas dengan variabel terikat. Jenis data penelitian adalah data sekunder yang di olah dengan menggunakan analisis statistika. Hasil penelitian ini : (1) Kredit Usaha Kecil (KUK) mempunyai pengaruh yang signifikan terhadap jumlah produksi usaha kecil di Sumatera Barat. Artinya semakin besar jumlah Kredit Usaha Kecil (KUK) yang disalurkan pihak perbankan besar kemungkinan jumlah produksi usaha kecil akan meningkat, (2) Kredit Usaha Kecil (KUK) mempunyai pengaruh yang signifikan terhadap jumlah tenaga kerja usaha kecil di Sumatera Barat. Artinya semakin besar jumlah Kredit Usaha Kecil (KUK) yang disalurkan pihak perbankan besar kemungkinan jumlah tenaga kerja usaha kecil akan meningkat. Penulis menyarankan kepada pihak perbankan agar lebih meningkatkan jumlah Kredit Usaha Kecil (KUK) kepada para pengusaha kecil, sehingga nantinya para pengusaha kecil dapat meningkatkan jumlah produksi dan penggunaan tenaga kerja hal ini berkemungkinan dapat meningkatkan perekonomian di Sumatera Barat.
Meiotic MCM Proteins Promote and Inhibit Crossovers During Meiotic Recombination

Crossover formation as a result of meiotic recombination is vital for the proper segregation of homologous chromosomes at the end of meiosis I. In many organisms, crossovers are generated through two crossover pathways: Class I and Class II. To ensure accurate crossover formation, meiosis-specific protein complexes regulate the degree to which each pathway is used. One such complex is the mei-mini-chromosome maintenance (MCM) complex, which contains MCM and MCM-like proteins REC (ortholog of Mcm8), MEI-217, and MEI-218. The mei-MCM complex genetically promotes Class I crossovers and inhibits Class II crossovers in Drosophila, but it is unclear how individual mei-MCM proteins contribute to crossover regulation. In this study, we perform genetic analyses to understand how specific regions and motifs of mei-MCM proteins contribute to Class I and II crossover formation, and distribution. Our analyses show that the long, disordered N-terminus of MEI-218 is dispensable for crossover formation, and that mutations that disrupt REC’s Walker A and B motifs differentially affect Class I and Class II crossover formation. In rec Walker A mutants, Class I crossovers exhibit no change but Class II crossovers are increased. However, in rec Walker B mutants, Class I crossovers are severely impaired and Class II crossovers are increased. These results suggest that REC may form multiple complexes that exhibit differential REC-dependent ATP-binding and -hydrolyzing requirements. These results provide genetic insight into the mechanisms through which mei-MCM proteins promote Class I crossovers and inhibit Class II crossovers.
Aedes aegypti Mosquitoes Use Their Legs to Sense DEET on Contact

Summary DEET (N, N-diethyl-meta-toluamide) is the most effective and widely used insect repellent, but its mechanism of action is both complex and controversial [ 1 ]. DEET acts on insect smell [ 2 , 3 , 4 , 5 , 6 ] and taste [ 7 , 8 , 9 , 10 , 11 ], and its olfactory mode of action requires the odorant co-receptor orco [ 2 , 3 , 6 ]. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but they are rapidly repelled after contacting DEET-treated skin [ 6 ]. DEET inhibits food ingestion by Drosophila melanogaster flies, and this repellency is mediated by bitter taste neurons in the proboscis [ 9 ]. Similar neurons were identified in the mosquito proboscis, leading to the hypothesis that DEET repels on contact by activating an aversive bitter taste pathway [ 10 ]. To understand the basis of DEET contact chemorepellency, we carried out behavioral experiments and discovered that DEET acts by three distinct mechanisms: smell, ingestion, and contact. Like bitter tastants, DEET is a feeding deterrent when ingested, but its bitterness per se does not fully explain DEET contact chemorepellency. Mosquitoes blood fed on human arms treated with high concentrations of bitters, but rapidly avoided DEET-treated skin and did not blood feed. Insects detect tastants both through their proboscis and legs. We show that DEET contact chemorepellency is mediated exclusively by the tarsal segments of the legs and not the proboscis. This work establishes mosquito legs as the behaviorally relevant contact sensors of DEET. These results will inform the search for molecular mechanisms mediating DEET contact chemorepellency and novel contact-based insect repellents.
Predicting Annotation Difficulty to Improve Task Routing and Model Performance for Biomedical Information Extraction.

Modern NLP systems require high-quality annotated data. For specialized domains, expert annotations may be prohibitively expensive; the alternative is to rely on crowdsourcing to reduce costs at the risk of introducing noise. In this paper we demonstrate that directly modeling instance difficulty can be used to improve model performance and to route instances to appropriate annotators. Our difficulty prediction model combines two learned representations: a ‘universal’ encoder trained on out of domain data, and a task-specific encoder. Experiments on a complex biomedical information extraction task using expert and lay annotators show that: (i) simply excluding from the training data instances predicted to be difficult yields a small boost in performance; (ii) using difficulty scores to weight instances during training provides further, consistent gains; (iii) assigning instances predicted to be difficult to domain experts is an effective strategy for task routing. Further, our experiments confirm the expectation that for such domain-specific tasks expert annotations are of much higher quality and preferable to obtain if practical and that augmenting small amounts of expert data with a larger set of lay annotations leads to further improvements in model performance.
Tree Drawings Revisited

We make progress on a number of open problems concerning the area requirement for drawing trees on a grid. We prove that (1) every tree of size n (with arbitrarily large degree) has a straight-line drawing with area $$n2^{O(\sqrt{\log \log n\log \log \log n})}$$ , improving the longstanding $$O(n\log n)$$ bound; (2) every tree of size n (with arbitrarily large degree) has a straight-line upward drawing with area $$n\sqrt{\log n}(\log \log n)^{O(1)}$$ , improving the longstanding $$O(n\log n)$$ bound; (3) every binary tree of size n has a straight-line orthogonal drawing with area $$n2^{O(\log ^*n)}$$ , improving the previous $$O(n\log \log n)$$ bound; (4) every binary tree of size n has a straight-line order-preserving drawing with area $$n2^{O(\log ^*n)}$$ , improving the previous $$O(n\log \log n)$$ bound; (5) every binary tree of size n has a straight-line orthogonal order-preserving drawing with area $$n2^{O(\sqrt{\log n})}$$ , improving the previous $$O(n^{3/2})$$ bound.
One-pot synthesis of [1,2,3]triazole-fused pyrazinopyridazindione tricycles by a ‘click and activate’ approach

Abstract Substituted [1,2,3]triazole-fused pyrazinopyridazindione tricycles were synthesized in a four-component, stepwise condensation. The key step in this one-pot process was a thermal [3+2] triazole formation which activated the adjacent position and set the stage for a subsequent tandem nucleophilic aromatic substitution/cyclization sequence.
Addition of Organometallic Nucleophiles to β-Keto Phosphonates.

The reaction of some Grignard reagents with β-keto phosphonates results in nucleophilic addition to the carbonyl group to afford β-hydroxy phosphonates with extension of the carbon skeleton. Additions of allylmagnesium reagents have proven particularly efficient, especially in the presence of BF3·OEt2. Reactions of allylic zinc reagents with β-keto phosphonates also gave the desired β-hydroxy phosphonates, often in even better yields. With crotyl and prenyl organometallic reagents, the reactions proceed with allylic transposition. Because these allylation reactions expand the functionality of the original substrate, various transformations can be conducted on the initial products to provide convenient access to a variety of new phosphonates.
Outsourcing Private RAM Computation.

We construct the rst schemes that allow a client to privately outsource arbitrary program executions to a remote server while ensuring that: (I) the client’s work is small and essentially independent of the complexity of the computation being outsourced, and (II) the server’s work is only proportional to the run-time of the computation on a random access machine (RAM), rather than its potentially much larger circuit size. Furthermore, our solutions are non-interactive and have the structure of reusable garbled RAM programs, addressing an open question of Lu and Ostrovsky (Eurocrypt 2013). We also construct schemes for an augmented variant of the above scenario, where the client can initially outsource a large private and persistent database to the server, and later outsource arbitrary program executions with read/write access to this database. Our solutions are built from non-reusable garbled RAM in conjunction with new types of reusable garbled circuits that are more ecient than prior solutions but only satisfy weaker security. For the basic setting without a persistent database, we can instantiate the required type of reusable garbled circuits from indistinguishability obfuscation or from functional encryption for circuits as a black-box. For the more complex setting with a persistent database, we can instantiate the required type of reusable garbled circuits using stronger notions of obfuscation. It remains an open problem to instantiate these new types of reusable garbled circuits under weaker assumptions, possibly avoiding obfuscation altogether. We also give several extensions of our results and techniques to achieve: schemes with eciency proportional to the input-specic RAM run-time, veriable outsourced RAM computation, functional encryption for RAMs, and a candidate obfuscator for RAMs.
A Titanium-Catalyzed Three-Component Coupling To Generate α,β-Unsaturated β-Iminoamines

The three-component coupling of an amine, alkyne, and isonitrile is facilitated by a titanium complex bearing the N,N-di(pyrrolyl-alpha-methyl)-N-methylamine (dpma) ligand. From this methodology, alpha,beta-unsaturated beta-iminoamines are generated regioselectively with many substrates and are available on multigram scales.
Recent advances in asymmetric synthesis with chiral imide auxiliaries

Progres en syhthese asymetrique : utilisation d'imides comme auxiliaires chiraux Les oxazolidinones chirales et leur derives sont des auxiliaires efficaces en synthese asymetrique. De nouvelles methodologies ontete developpees, notamment des alkylations de composes glycoliques et des reactions d'aldol utilisant une quantite catalytique de metal, produisant les diastereoisomeres anti. Quelques exemples recents et innovateurs d'utilisations de ce type d'auxiliaires en synthese totale sont aussi abordes.
Thiourea catalysis of NCS in the synthesis of chlorohydrins

Thiourea catalysis of reactions utilizing N-succinimides is demonstrated with NCS chlorination of olefins in the presence of water to afford chlorohydrins.
BIOPOLYMER SYNTHESIS ON SOLID SUPPORTS

The concept of solid phase synthesis began as a new approach to the preparation of peptides, but has been extended to the synthesis of polynucleotides, polysaccharides, polyamides and a variety of other classes of compounds. The solid support simplifies and accelerates the synthetic process, aids the separation of reagents and by-products, and reduces problems of insolubility of intermediates. The synthesis may involve a stepwise addition of monomer units or the condensation of preformed oligomer fragments. Large numbers of peptides and several small proteins have been synthesized by the solid phase method. To facilitate the synthesis We have developed a new, more acid-stable attachment of the peptide to the polystyrene support, in which the chain is anchored through a hydroxymethylphenylacetamidomethyl group. Alternatively, the peptide chain can be anchored through a more labile alkoxybenzyl ester linkage, if the very acid-sensitive Bpoc group is used for Nα-protection. The ideal design for a multi-step synthesis will depend on a combination of protecting groups that are removable by completely independent reaction mechanisms. Such a system is called orthogonal. A new amino protecting group, the dithiasuccinoyl (Dts) group, has been designed for that purpose. It is removed by reduction, but is stable to acids and photolysis and can be used in conjunction with these two orthogonal modes of deprotection. The synthesis of biopolymers on solid supports was illustrated by studies of the role of arginine in the neurotoxin, apamin, and of the substrate specificity of a histone deacetylase and by a recent synthesis of crystalline glucagon.
Novel polyethylene glycol derivatives of melatonin and serotonin. Ligands for conjugation to fluorescent cadmium selenide/zinc sulfide core shell nanocrystals

This paper describes the synthesis and characterisation of derivatives of melatonin and serotonin that may be attached to highly fluorescent cadmium selenide/zinc sulfide core shells nanocrystals for use in biological assays and fluorescence imaging applications.
Antibodies Against Egg- and Cell-Grown Influenza A(H3N2) Viruses in Adults Hospitalized During the 2017-2018 Influenza Season.

Background Influenza vaccine effectiveness was low in 2017-2018, yet circulating influenza A(H3N2) viruses were antigenically similar to cell-grown vaccine strains. Notably, most influenza vaccines are egg propagated. Methods Serum specimens were collected shortly after illness onset from 15 influenza A(H3N2) virus-infected cases and 15 uninfected hospitalized adults. Geometric mean titers against egg- and cell-grown influenza A/Hong Kong/4801/2014(H3N2) virus vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by a microneutralization (MN) assay. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression. Results MN titers against egg-grown influenza A/Hong Kong virus were significantly higher among vaccinated individuals (173 vs 41; P = 0.01). In unadjusted models, a 2-fold increase in titers against egg-grown influenza A/Hong Kong virus was not significantly protective (29% reduction; P = .09), but a similar increase in the cell-grown influenza A/Washington virus antibody titer (3C.2a2) was protective (60% reduction; P = .02). Higher egg-grown influenza A/Hong Kong virus titers were not significantly associated with infection, when adjusted for antibody titers against influenza A/Washington virus (15% reduction; P = .61). A 54% reduction in the odds of infection was observed with a 2-fold increase in titer against influenza A/Washington virus (P = not significant), adjusted for the titer against egg-grown influenza A/Hong Kong virus titer. Conclusion Individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain and lower titers against circulating viruses. Titers against circulating but not egg-adapted strains were correlated with protection.
An improved synthesis of hydroxymethyl bipyridines

Abstract This account describes quick and efficient syntheses of 4,4′-bis(hydroxymethyl)-2,2′-bipyridine and 4-hydroxymethyl-2,2′-bipyridine from 4,4′-dimethyl-2,2′-bipyridine and 4-methyl-2,2′-bipyridine, respectively, via (trimethylsilyl)methyl-, bromomethyl-, and acetoxymethyl- intermediates.
Synthesis, crystal and electronic structures of the new Zintl phases Ba3Al3Pn5 (Pn = P, As) and Ba3Ga3P5.

The new Zintl compounds Ba3Al3P5, Ba3Al3As5, and Ba3Ga3P5 have been synthesized using molten metal fluxes. They are isoelectronic and isotypic, crystallizing with a novel rhombohedral structure type in the space group R3c with unit cell constants a = 14.5886(9) A, c = 28.990(3) A for Ba3Al3P5, a = 14.613(3) A, c = 28.884(8) A for Ba3Ga3P5, and a = 14.9727(13) A, c = 29.689(4) A for Ba3Al3As5, respectively. The structures are based on TrPn4 (Tr = Al, Ga; Pn = P, As) tetrahedra that share both edges and corners, leading to intricate arrangements embodied in the [Tr4Pn9]15– and [Tr3Pn6]9– strands, interconnected by dimeric [Tr2Pn6]12– units. The Ba2+ cations reside within cylindrical channels within the polyanionic framework and provide the valence electrons needed for Tr–Pn covalent bonding. In spite of the large and complex structure, there are no homoatomic Tr–Tr or Pn–Pn interactions, hence, the structures can be readily rationalized in the context of the Zintl–Klemm formalism as follows [Ba2+]3[Tr3+]3[...
Cyclic sulfonamides via the ring-closing metathesis reaction

Abstract The first examples of ring-closing metathesis (RCM) reactions on allyl- and vinylsulfonamide templates 1 and 2 catalyzed by the Grubbs ruthenium alkylidene 3 are described. The rate of cyclization of these reactions are sensitive to simple olefin substitution. These RCM reactions yield novel cyclic allyl- and vinylsultams 4 and 5 and represent our initial efforts toward the construction of novel sulfonamides.
Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration.

A new class of viral mammalian Slow Progressive Hidden INfections of variable (X) latency ("SPHINX") DNAs, represented by the 1.8 and 2.4 kb nuclease-protected circular elements, were discovered in highly infectious cytoplasmic particles isolated from Creutzfeldt-Jakob Disease (CJD) and scrapie samples. These DNAs contained replication initiation sequences (REPs) with approximately 70% homology to those of environmental Acinetobacter phage. Antibodies against REP peptides from the 1.8 kb DNA highlighted a 41 kDa protein (spx) on Western blots, and in situ studies previously revealed its peripheral tissue expression, for example, in pancreatic islet cells, keratinocytes, kidney tubules, and oocytes but not pancreatic exocrine cells, alveoli, and striated muscle. To determine if spx concentrated in specific neurons and synapses, and also maintained a conserved pattern of architectural organization in mammalian brains, we evaluated mouse, rat, hamster, guinea pig (GP), and human samples. Most outstanding was the cross-species concentration of spx in huge excitatory synapses of mossy fibers and small internal granule neuron synapses, the only excitatory neuron within the cerebellum. Spx also localized to excitatory glutamate type synapses in the hippocampus, and both cerebellar and hippocampal synaptic spx was demonstrable ultrastructurally. Studies of two well-characterized models of sporadic CJD (sCJD) revealed novel spx pathology. Vacuolar loss of cerebellar synaptic complexes, thinning of the internal granule cell layer, and fibrillar spx accumulations within Purkinje neurons were prominent in sCJD GP brains. In rats, comparable spx fibrillar changes appeared in hippocampal pyramidal neurons, and they preceded prion protein misfolding. Hence, spx is an integral player in progressive neurodegeneration. The evolutionary origin, spread, and neuropathology of SPHINX 1.8 REP sequences opens another unanticipated chapter for mammalian symbiotic interactions with environmental microbes.
Immortalization of Different Breast Epithelial Cell Types Results in Distinct Mitochondrial Mutagenesis.

Different phenotypes of normal cells might influence genetic profiles, epigenetic profiles, and tumorigenicities of their transformed derivatives. In this study, we investigate whether the whole mitochondrial genome of immortalized cells can be attributed to the different phenotypes (stem vs. non-stem) of their normal epithelial cell originators. To accurately determine mutations, we employed Duplex Sequencing, which exhibits the lowest error rates among currently-available DNA sequencing methods. Our results indicate that the vast majority of the observed mutations of the whole mitochondrial DNA occur at low-frequency (rare mutations). The most prevalent rare mutation types are C→T/G→A and A→G/T→C transitions. Frequencies and spectra of homoplasmic point mutations are virtually identical between stem cell-derived immortalized (SV1) cells and non-stem cell-derived immortalized (SV22) cells, verifying that both cell types were derived from the same woman. However, frequencies of rare point mutations are significantly lower in SV1 cells (5.79 × 10−5) than in SV22 cells (1.16 × 10−4). The significantly lower frequencies of rare mutations are aligned with a finding of longer average distances to adjacent mutations in SV1 cells than in SV22 cells. Additionally, the predicted pathogenicity for rare mutations in the mitochondrial tRNA genes tends to be lower (by 2.5-fold) in SV1 cells than in SV22 cells. While four known/confirmed pathogenic mt-tRNA mutations (m.5650 G>A, m.5521 G>A, m.5690 A>G, m.1630 A>G) were identified in SV22 cells, no such mutations were observed in SV1 cells. Our findings suggest that the immortalization of normal cells with stem cell features leads to decreased mitochondrial mutagenesis, particularly in RNA gene regions. The mutation spectra and mutations specific to stem cell-derived immortalized cells (vs. non-stem cell derived) have implications in characterizing the heterogeneity of tumors and understanding the role of mitochondrial mutations in the immortalization and transformation of human cells.
p53 is required for female germline stem cell maintenance in P-element hybrid dysgenesis.

Abstract Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain transposable elements in the Drosophila germline. Particularly extreme is the hybrid dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic female ovaries often contain few or no germline cells. Those offspring that are produced from dysgenic germlines exhibit high rates of de novo mutation and recombination, implicating transposition-associated DNA damage as the cause of germline loss. However, how this loss occurs, in terms of the particular cellular response that is triggered (cell cycle arrest, senescence, or cell death) remains poorly understood. We demonstrate that two components of the DNA damage response, Checkpoint kinase 2 and its downstream target p53, determine the frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. We further show that p53 is strongly induced in the germline stem cells (GSCs) of dysgenic females, and is required for their maintenance. Our observations support the critical role for p53 in conferring tolerance of transposable element activity in stem cells.
Heats of Formation and Bond Energies of the H(3−n)BXn Compounds for (X = F, Cl, Br, I, NH2, OH, and SH)

Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted for the borane compounds H(3−n)BXn for (X = F, Cl, Br, I, NH2, OH, and SH) and various radicals from coupled cluster theory (CCSD(T)) calculations with an effective core potential correlation-consistent basis set for I. In order to achieve near chemical accuracy (±1.5 kcal/mol), three corrections were added to the complete basis set binding energies calculated from frozen core coupled cluster theory energies: a correction for core-valence effects, a correction for scalar relativistic effects, and a correction for first-order atomic spin−orbit effects. Vibrational zero point energies were computed at the MP2 level. The calculated heats of formation are in excellent agreement with the available experimental data for the closed shell molecules, but show larger differences with the reported “experimental” values for the BX2 radicals. The heats of formation of the BX2 radicals were also calculated at the G3(MP2) level of theory, an...
Platinum(II)-catalyzed addition of alcohols to alkynes

A simple, high-yielding synthesis of acetals from the platinum(II)-catalyzed addition of alcohols to alkynes is described. The regioselectivity of the method and its mechanism are also discussed.
Whole-genome characterization in pedigreed non-human primates using genotyping-by-sequencing (GBS) and imputation

Rhesus macaques are widely used in biomedical research, but the application of genomic information in this species to better understand human disease is still in its infancy. Whole-genome sequence (WGS) data in large pedigreed macaque colonies could provide substantial experimental power for genetic discovery, but the collection of WGS data in large cohorts remains a formidable expense. Here, we describe a cost-effective approach that selects the most informative macaques in a pedigree for 30X WGS, followed by low-cost genotyping-by-sequencing (GBS) at 30X on the remaining macaques in order to generate sparse genotype data at high accuracy. Dense variants from the selected macaques with WGS data are then imputed into macaques having only sparse GBS data, resulting in dense genome-wide genotypes throughout the pedigree. We developed GBS for the macaque genome using a digestion with PstI, followed by sequencing of size-selected fragments at 30X coverage. From GBS sequence data collected on all individuals in a 16-member pedigree, we characterized high-confidence genotypes at 22,455 single nucleotide variant (SNV) sites that were suitable for guiding imputation of dense sequence data from WGS. To characterize dense markers for imputation, we performed WGS at 30X coverage on nine of the 16 individuals, yielding 10,193,425 high-confidence SNVs. To validate the use of GBS data for facilitating imputation, we initially focused on chromosome 19 as a test case, using an optimized panel of 833 sparse, evenly-spaced markers from GBS and 5,010 dense markers from WGS. Using the method of “Genotype Imputation Given Inheritance” (GIGI), we evaluated the effects on imputation accuracy of 3 different strategies for selecting individuals for WGS, including 1) using “GIGI-Pick” to select the most informative individuals, 2) using the most recent generation, or 3) using founders only. We also evaluated the effects on imputation accuracy of using a range of from 1 to 9 WGS individuals for imputation. We found that the GIGI-Pick algorithm for selection of WGS individuals outperformed common heuristic approaches, and that genotype numbers and accuracy improved very little when using >5 WGS individuals for imputation. Informed by our findings, we used 4 macaques with WGS data to impute variants at up to 7,655,491 sites spanning all 20 autosomes in the 12 remaining macaques, based on their GBS genotypes at only 17,158 loci. Using a strict confidence threshold, we imputed an average of 3,680,238 variants per individual at >99 % accuracy, or an average 4,458,883 variants per individual at a more relaxed threshold, yielding >97 % accuracy. We conclude that an optimal tradeoff between genotype accuracy, number of imputed genotypes, and overall cost exists at the ratio of one individual selected for WGS using the GIGI-Pick algorithm, per 3–5 relatives selected for GBS. This approach makes feasible the collection of accurate, dense genome-wide sequence data in large pedigreed macaque cohorts without the need for more expensive WGS data on all individuals.
Building unit and topological evolution in the hydrothermal DABCO-U-F system.

Compounds NDUF-1 ([C6H14N2](UO2)2F6; P21/c, a = 6.9797(15) A, b = 8.3767(15) A, c = 23.760(5) A, β = 91.068(4)°, V = 1388.9(5) A3, Z = 4), NDUF-2 ([C6H14N2]2(UO2)2F5UF7·H2O), NDUF-3 ((NH4)7U6F31; R3, a = 15.4106(8) A, c = 10.8142(8) A, V = 2224.1(2) A3, Z = 3), and NDUF-4 ([NH4]U3F13) have been synthesized hydrothermally from fixed composition reactant mixtures over variable time periods [DABCO (C6H12N2), UO2(NO3)2·6H2O, HF, and H2O; 2−14 days]. Observed is a systematic evolution of the structural building units within these materials from the UO2F5 pentagonal bipyramid in NDUF-1 and -2 to the UF8 trigonal prism in NDUF-2 and finally to the UF9 polyhedron in NDUF-3 and -4 as a function of reaction time. Coupled to this coordination change is a reduction of UVI to UIV as well as a breakdown of the organic structure-directing agent from DABCO to NH4+. These processes contribute to a structural transition from layered topologies (NDUF-1) to chain (NDUF-2), back to layered (NDUF-3), and ultimately to framewo...
Steric and electronic effects on the partitioning of a persulfinyl intermediate along the physical quenching and chemical reaction channels

Abstract The rate constants, kT, kr, and kQ, corresponding to the substrate induced total removal, chemical removal, and physical removal of singlet oxygen, respectively, have been measured for a series of sulfenamides. The structural effects on the partitioning of the persulfinamide intermediate along the chemical and physical deactivation pathways is discussed.
Electrochemically Generated Organometallic Reagents and Site-Selective Synthesis on a Microelectrode Array

Organometallic reagents and catalysts are powerful tools for site-selectively modifying the surface of a microelectrode array. In this context, the reagents or catalysts are generated at the electrodes in the array and then destroyed again in the solution above the array. In this way, they can be used to conduct reactions that are confined to the regions of the array immediately surrounding the electrodes used. In the review presented, this general strategy is applied to a series of organometallic reactions that serve to illustrate the scope of synthetic chemistry possible.
Giant cyclophanes built from polyphenyl aromatic substructures

Two very large cyclophanes (3, C132H92O8S4; 4, C172H120O8S4) were prepared by means of short syntheses (∼5 steps) from commercial starting materials. In each of these cyclophanes, two octaphenylnaphthalene subunits or two 1,3-bis(pentaphenylphenyl)benzene subunits were tethered to form the final macrocycle. X-ray analysis of 3 shows it to have a collapsed conformation, but molecules of 4 have large central cavities which are aligned in the crystal to form wide, solvent-containing channels.
A Flexible Enantioselective Synthesis of the Isofurans

Recently, the isolation of a new class of human arachidonic acid tetrahydrofuran oxidation products, the isofurans (IsoF's), was reported. These new compounds are available from natural sources only in microgram quantities as mixtures. The enantioselective preparation of a versatile epoxide intermediate and its conversion to the enantiomerically pure isofurans SC-Δ13-9-IsoF and 15-epi-SC-Δ13-9-IsoF are described. This synthesis will make these metabolites available for physiological evaluation.
Asymmetric aldol reaction with diisopinocampheyl enolborinates of propionates.

A convenient and general, reagent-controlled, diastereo- and enantioselective aldol reaction of diisopinocampheylboron enolates of esters, followed by reduction, has been developed as an alternative to crotylboration-ozonolysis. This protocol was then exploited for the double diastereoselective synthesis of the C11−C17 subunit of (−)-dictyostatin.
(+)-Phorboxazole A synthetic studies. Identification of a series of highly cytotoxic C(45-46) analogues.

Effective, scalable total syntheses and biological evaluation of six phorboxazole A analogues (1−6) have been achieved. Importantly, the C(45−46)-saturated, C(45−46)-alkenyl, and the C(45−46)-E-chloroalkenyl congeners (4, 5, and 6, respectively) reveal low nanomolar tumor cell growth inhibitory activity (GI50's) similar to or, in some cell lines, greater than that of the phorboxazoles across a diverse panel of human cancer cell lines.
A new synthesis of α-methylserine by nucleophilic ring-opening of N-sulfonyl aziridines☆

Abstract Conversion of tritylated 2-methylglycidol to the corresponding aziridine occurs by Staudinger cyclization of the intermediate azido alcohol. After N -sulfonylation with Ses-Cl and ring-opening with benzyl alcohol, oxidation of the primary alcohol provides N , O -bisprotected α-methylserine directly suitable for repetitive peptide synthesis. This sequence represents a general enantioselective protocol for the synthesis of α-methylserine and other α,α-disubstituted amino acids.
Condensation Versus Hydroamination for the Direct, Catalytic Synthesis of Tetrasubstituted Propargylamines

Multicomponent couplings of carbonyls, amines, and nucleophiles provide a wide array of trisubstituted carbons bearing amines but tetrasubstituted products are rarely formed. Cooperative copper/titanium catalysis under solvent-free conditions is required to overcome the barrier to condensation of a ketone with an amine and subsequent alkynylation. An alternative mode of accessing ket­imines is the Markovnikov hydroamination of alkynes. Heating a simple copper salt with an amine and a terminal alkyne rapidly produces tetrasubstituted propargylic amines via tandem hydroamination–alkynylation.
Is the statistic value all we should care about in neuroimaging

Here we address an important issue that has been embedded within the neuroimaging community for a long time: the absence of effect estimates in results reporting in the literature. The statistic value itself, as a dimensionless measure, does not provide information on the biophysical interpretation of a study, and it certainly does not represent the whole picture of a study. Unfortunately, in contrast to standard practice in most scientific fields, effect (or amplitude) estimates are usually not provided in most results reporting in the current neuroimaging publications and presentations. Possible reasons underlying this general trend include (1) lack of general awareness, (2) software limitations, (3) inaccurate estimation of the BOLD response, and (4) poor modeling due to our relatively limited understanding of FMRI signal components. However, as we discuss here, such reporting damages the reliability and interpretability of the scientific findings themselves, and there is in fact no overwhelming reason for such a practice to persist. In order to promote meaningful interpretation, cross validation, reproducibility, meta and power analyses in neuroimaging, we strongly suggest that, as part of good scientific practice, effect estimates should be reported together with their corresponding statistic values. We provide several easily adaptable recommendations for facilitating this process.
Convenient synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides

We report a facile one-pot, three-step synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides via condensation of 2-p-methoxybenzylamino-4-acetylpyridine with phenylacetylthioureas.
Colossal Magnetoresistance in a Rare Earth Zintl Compound with a New Structure Type: EuIn2P2

Single crystals of a new Zintl compound, EuIn2P2, were grown from indium metal as a flux solvent. The compound crystallizes in the hexagonal P6(3)/mmc space group with a unit cell of a = 4.0829(6) A, c = 17.595(4) A, and Z = 2. It contains alternating Eu2+ layers and [In2P2]2- layers. This compound is paramagnetic at high temperatures with a magnetic transition at 24 K. In the magnetically ordered state, it shows large magnetic anisotropy. The temperature-dependent resistivity of this compound suggests interaction between conduction electrons and local spins. Negative colossal magnetoresistance of up to −398% (MR = {[ρ(H) − ρ(0)]/ρ(H)} × 100%) at 5 T is observed at 24 K.
Synthesis of 2‐phenylquinolin‐4‐amines substituted with diverse amino and aminoalkyl groups

Facile synthetic approaches to 2-phenylquinolin-4-amines containing an aminoalkyl group at N4 of the quinolin-4-amine and amino or aminoalkyl groups at the phenyl moiety are presented.
INTRAMOLECULAR 4+3 CYCLOADDITIONS. ALLYLIC SULFONES AS PRECURSORS TO VINYLTHIONIUM IONS

Summary Treatment of a THF solution of ( E )-3 with n-BuLi followed by quenching with an electrophile generally results in regioselective alkylation alpha to the sulfone with the alkene possessing ( E ) stereochemistry in the major product. High selectivity for the ( E ) alkylation product can be achieved in the presence of small amounts of HMPA. When those ( E ) alkylation products possessing a diene moiety in the side chain are treated with Lewis acids, 4+3 cycloaddition products are formed in good to excellent yields.
α-Aminoamides as ligands in Goldberg amidations

Abstract α-Aminoamides are shown to be useful as ligands in Goldberg amidations. A number of α-aminoamides are examined and the importance of substitution on the α-aminoamides is explored. Acetamide is focused on as the nucleophilic coupling partner due to its low cost, stability and convenience as a protecting group. The initial substrate scope for these catalysts is explored and includes electronically activated and deactivated aryl bromides, however o-substituted aryl bromides are problematic.
The “Future Is Now” Bias: Anchoring and (Insufficient) Adjustment When Predicting the Future from the Present

Abstract In the present research, we document a novel forecasting bias, which we term the “future is now” (FIN) bias. Specifically, we show that people tend to believe that the future will mirror the present, even when such a belief is unfounded. That is, people overestimate the chances that whatever is happening now, will happen in the future, even when the (known) explicit probabilities of future outcomes contradict such a belief. This appears to be driven by an anchoring and (insufficient) adjustment process, whereby initial beliefs about the future are heavily influenced by the present circumstances, and then subsequent beliefs are not sufficiently adjusted once the probabilities of future outcomes are learned. Across nine studies (employing over 3800 participants), we demonstrate the FIN bias in a variety of forecasting contexts, show that it manifests in incentive compatible settings, and provide evidence in support of an anchoring and (insufficient) adjustment mechanistic account.
Exploration by Distributional Reinforcement Learning.

We propose a framework based on distributional reinforcement learning and recent attempts to combine Bayesian parameter updates with deep reinforcement learning. We show that our proposed framework conceptually unifies multiple previous methods in exploration. We also derive a practical algorithm that achieves efficient exploration on challenging control tasks.
Distributed Computing with Adaptive Heuristics

We use ideas from distributed computing to study dynamic environments in which computational nodes, or decision makers, follow adaptive heuristics (16), i:e., simple and unsophisticated rules of behavior, e.g., repeatedly \best replying" to others' actions, and minimizing \regret", that have been extensively studied in game theory and economics. We explore when convergence of such simple dynamics to an equilibrium is guaranteed in asynchronous computational environments, where nodes can act at any time. Our research agenda, distributed computing with adaptive heuristics, lies on the borderline of computer science (including distributed computing and learning) and game theory (including game dynamics and adaptive heuristics). We exhibit a general non- termination result for a broad class of heuristics with bounded recall|that is, simple rules of behavior that depend only on recent history of interaction between nodes. We consider implications of our result across a wide variety of interesting and timely applications: game theory, circuit design, social networks, routing and congestion control. We also study the computational and communication complexity of asynchronous dynamics and present some basic observations regarding the efiects of asynchrony on no-regret dynamics. We believe that our work opens a new avenue for research in both distributed computing and game theory.