Rh(I)-Catalyzed Regio- and Enantioselective Ring Opening of Vinyl Cyclopropanes.

We describe a Rh(I) catalyzed asymmetric ring opening of racemic vinyl cyclopropanes using aryl boronic acids as C-nucleophiles. When ferrocene-based chiral bisphosphines are used as ligands, the products are obtained with regioselectivities typically 99:1 r.r. and ee's generally between 88 and 96%. A wide range of aryl boronic acids can be used, and the products can be converted into a variety of targets. Preliminary mechanistic studies indicate that Zn(OTf)2 plays a significant role in the reaction by promoting rhodium-ligand complex formation and accelerating the reaction. We expect this method and these mechanistic insights to be useful in the development of new asymmetric methods.

Effect of artificial gravity on neurocognitive performance during head-down tilt bedrest.

This study evaluated the acute and chronic effects of intermittent and continuous Artificial Gravity (AG) on cognitive performance during 60 days of Head-down tilt bedrest (HDTBR), a well-established ground-based spaceflight analogue method. Participants were randomly assigned to three groups: intermittent AG, continuous AG, and HDTBR control group without AG exposure. Task performance and electrophysiological measures of attention and working memory were investigated during Simple and Complex tasks in the Visual and the Auditory modality. Compared to baseline, faster reaction time and better accuracy was present during HDTBR regarding the Complex tasks, however, the practice effect was diminished in the three HDTBR groups compared to an ambulatory control group. Brain potentials showed a modality-specific decrease, as P3a was decreased only in the Auditory, while P3b decreased in the Visual modality. No evidence for acute or chronic AG-related cognitive impairments during HDTBR was found.

Optimization of the Antibacterial Spectrum and the Developability Profile of the Novel-Class Natural Product Corramycin.

Corramycin 1 is a novel zwitterionic antibacterial peptide isolated from a culture of the myxobacterium Corallococcus coralloides. Though Corramycin displayed a narrow spectrum and modest MICs against sensitive bacteria, its ADMET and physchem profile as well as its high tolerability in mice along with an outstanding in vivo efficacy in an Escherichia coli septicemia mouse model were promising and prompted us to embark on an optimization program aiming at enlarging the spectrum and at increasing the antibacterial activities by modulating membrane permeability. Scanning the peptidic moiety by the Ala-scan strategy followed by key stabilization and introduction of groups such as a primary amine or siderophore allowed us to enlarge the spectrum and increase the overall developability profile. The optimized Corramycin 28 showed an improved mouse IV PK and a broader spectrum with high potency against key Gram-negative bacteria that translated into excellent efficacy in several in vivo mouse infection models.

Performance evaluation of a novel multi-pinhole collimator on triple-NaI-detector SPECT/CT for dedicated myocardial imaging.

BACKGROUND: In this study we evaluated the imaging capabilities of a novel Multi-pinhole collimator (MPH-Cardiac) specially designed for nuclear cardiology imaging on a Triple-NaI-detector based SPECT/CT system. METHODS: 99mTc point source measurements covering the field of view (FOV) were used to determine tomographic sensitivity (TSpointsource) and spatial resolution. Organ-size tomographic sensitivity (TSorgan) was measured with a left ventricle (LV) phantom filled with typical myocardial activity of a patient scan. Reconstructed image uniformity was measured with a 140 mm diameter uniform cylinder phantom. Using the LV phantom once filled with 99mTc and after with 123I, Contrast-to-noise ratio (CNR) was measured on the reconstructed images by ROI analysis on the myocardium activity and on the LV cavity. Furthermore, a polar map analysis was performed determining Spill-Over-Ratio in water (SORwater) and image noise. The results were compared with that of a dual-head parallel-hole low energy high resolution (LEHR) collimator system. A patient with suspected coronary artery disease (CAD) was scanned on the LEHR system using local protocol of 16 min total acquisition time, followed by a 4-min MPH-Cardiac scan. RESULTS: Peak TSpointsource was found to be 1013 cps/MBq in the axial center of the FOV while it was decreasing toward the radial edges. TSorgan in the CFOV was found to be 134 cps/MBq and 700 cps/MBq for the LEHR and MPH-Cardiac, respectively. Average spatial resolution throughout the FOV was 4.38 mm FWHM for the MPH-Cardiac collimator. Reconstructed image uniformity values were found to be 0.292% versus 0.214% for the LEHR and MPH-Cardiac measurements, respectively. CNR was found to be higher in case of MPH-Cardiac than for LEHR in case of 99mTc (15.5 vs. 11.7) as well as for 123I (13.5 vs. 8.3). SORwater values were found to be 28.83% and 21.1% for the 99mTc measurements, and 31.44% and 24.33% for the 123I measurements for LEHR and MPH-Cardiac, respectively. Pixel noise of the 99mTc polar maps resulted in values of 0.38% and 0.24% and of the 123I polar maps 0.62% and 0.21% for LEHR and MPH-Cardiac, respectively. Visually interpreting the patient scan images, MPH-Cardiac resulted in better image contrast compared to the LEHR technique with four times shorter scan duration. CONCLUSIONS: The significant image quality improvement achieved with dedicated MPH-Cardiac collimator on triple head SPECT/CT system paves the way for short acquisition and low-dose cardiovascular SPECT applications.

Are head-down tilt bedrest studies capturing the true nature of spaceflight-induced cognitive changes? A review.

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions.

Sensitivity study of C/O logging measurements by Monte Carlo method.

Carbon oxygen ratio (C/O) logging has great importance in the accurate determination of hydrocarbon saturation in the reservoir region. This measurement is independent of the salinity of the formation water, unlike alternative logging methods. Analysis of the measurement requires modelling of the time-dependent coupled neutron-gamma field produced by the tool, which is most efficiently done by the Monte Carlo (MC) method. MC simulation can be used to generate the gamma spectrum at the detectors of the probe for a variety of rock physics conditions and borehole environments and thus the C/O can be determined by the processing of the simulated gamma spectrum. The simulation results are used to derive the interpretation diagrams for the basic petrophysical effects and to investigate the role of the side effects. Considering the industrial practice of log evaluation, the resolution and limitations of the method is quantified in the measurement space by defining a goodness factor based on the area of the interpretation chart. The focus of this paper is on detector arrangement, but it also covers the effect of porosity, lithology, and the casing.

Persistent deterioration of visuospatial performance in spaceflight.

Although human adaptation to spaceflight has been studied for decades, little is known about its long-term effects on brain and behavior. The present study investigated visuospatial performance and associated electrophysiological responses in astronauts before, during, and after an approximately half-year long mission to the International Space Station. Here we report findings demonstrating that cognitive performance can suffer marked decrements during spaceflight. Astronauts were slower and more error-prone on orbit than on Earth, while event-related brain potentials reflected diminished attentional resources. Our study is the first to provide evidence for impaired performance during both the initial (~ 8 days) and later (~ 50 days) stages of spaceflight, without any signs of adaptation. Results indicate restricted adaptability to spaceflight conditions and calls for new research prior to deep space explorations.

Catalytic Asymmetric Diarylphosphine Addition to α-Diazoesters for the Synthesis of P-Stereogenic Phosphinates via P*-N Bond Formation.

The asymmetric catalytic P-H addition of racemic secondary phosphines to electrophilic α-diazoesters via P*-N bond formation is disclosed for the first time. Interaction between the diazoester and the palladium catalyst resulted in the unusually enhanced electrophilic ability of the terminal nitrogen in the diazo functionality, as opposed to the commonly expected formation of a metal carbene by nitrogen elimination. Further derivatization of the generated phosphinic hydrazones provided access to enantioenriched P-stereogenic diarylphosphinates via a simple transformation.

Tandem double hydrophosphination of α,ß,γ,δ-unsaturated-1,3-indandiones: diphosphine synthesis, mechanistic investigations and coordination chemistry.

A metal-free tandem double hydrophosphination of extended conjugated indandiones has been established. Mechanistic investigations confirmed the consecutive manner of the nucleophilic addition reaction. Complexation of the generated keto-diphosphine resulted in the formation of an unexpected tridentate bridging ligand with an anionic P,O-bidentate and a neutral P-monodentate coordination mode on two palladium units. In the presence of an external chiral auxiliary, the coordinated diphosphines could be separated into their enantiomeric forms.

Differential impact of acute hypoxia on event related potentials: impaired task-irrelevant, but preserved task-relevant processing and response inhibition.

The current study investigated how experimentally induced acute normobaric hypoxia affects attentional control functions during easy, monotonous visual sustained attention and response inhibition (modified Continuous Performance Task) and executive control tasks (number-size Stroop task). Along with behavioral efficiency, task-relevant and task-irrelevant information processing were investigated by measuring event related brain potentials (ERP) evoked by target stimuli (Target P3), task-relevant stimuli with no response needed (NoGo P3), and task-irrelevant novel stimuli (Novelty P3) during acute hypoxia exposure. Normobaric hypoxia was induced by adjusting the O2 content of the breathing mixture to obtain 80% peripheral oxygen saturation, equivalent of 5500 m above sea level. Here we report decreased Novelty P3 during acute normobaric hypoxia exposure, while Target P3 and NoGo P3, as well as behavioral efficiency remained intact. Our paper is the first to provide evidence for impaired novelty processing along with intact task-relevant information processing and response inhibition during normobaric hypoxic exposure.

Scope and limitation of propylene carbonate as a sustainable solvent in the Suzuki-Miyaura reaction.

The Suzuki-Miyaura reaction is one of the most used transformations in drug research. Thus making this reaction more sustainable is of considerable current interest. Here we show that propylene carbonate (PC) can be used as a solvent for the Suzuki-Miyaura reaction. PC is one of the greenest solvents since it is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact allowed the isolation of several novel compounds which were generated under prominently green conditions.

Cognitive resilience after prolonged task performance: an ERP investigation.

Deleterious consequences of cognitive fatigue might be avoided if people respond with increased effort to increased demands. In this study, we hypothesized that the effects of fatigue would be more pronounced in cognitive functions reflecting compensatory effort. Given that the P3a event-related potential is sensitive to the direction and amount of attention allocated to a stimulus array, we reasoned that compensatory effort would manifest in increased P3a amplitudes. Therefore, we compared P3a before (pre-test) and after (post-test) a 2 h long cognitively demanding (fatigue group, n = 18) or undemanding task (control group, n = 18). Two auditory tasks, a three-stimulus novelty oddball and a duration discrimination two-choice response task were presented to elicit P3a. In the fatigue group, we used the multi-attribute task battery as a fatigue-inducing task. This task draws on a broad array of attentional functions and imposed considerable workload. The control group watched mood-neutral documentary films. The fatigue manipulation was effective as subjective fatigue increased significantly in the fatigue group compared to controls. Contrary to expectations, however, fatigue failed to affect P3a in the post-test phase. Similar null effects were obtained for other neurobehavioral measures (P3b and behavioral performance). Results indicate that a moderate increase in subjective fatigue does not hinder cognitive functions profoundly. The lack of objective performance loss in the present study suggests that the cognitive system can be resilient against challenges instigated by demanding task performance.

Dissociated Components of Executive Control in Acute Hypobaric Hypoxia.

INTRODUCTION: The neurocognitive effects of acute hypobaric hypoxia are still largely unknown. This study was designed to test the hypothesis that executive control, an important component of cognition, is especially vulnerable to hypoxia. METHODS: Subjects participated in a simulated hypobaric chamber flight to 5500 m. Four auditory tasks were presented before, during, and after hypoxia: 1) Voice, and 2) Name variant of the Stroop task (both measuring conflict resolution); 3) go/no-go task (GNG; measuring inhibition); and 4) two-choice reaction time task (CRT; which is a noninhibitory control task). RESULTS: The Stroop effect increased during hypoxia: in the Voice Stroop it increased from 49.4 to 83.6 ms for reaction time and from 4.1 to 12.3% for accuracy; in the Name Stroop from 43.5 to 82.9 ms for reaction time (accuracy remained unchanged). Accuracy declined from 82.3 to 75.0% in CRT, and from 85.8 to 77.5% (averaged over stimulus types) in the GNG task. Importantly, accuracy decreased similarly to go and no-go stimuli in the GNG task, revealing unaffected inhibition. DISCUSSION: The findings suggest that tasks requiring conflict resolution are more likely to be impaired than tasks requiring inhibition of response. Furthermore, our results provide evidence for the distinct nature of inhibitory control functions.Takács E, Czigler I, Pató LG, Balázs L. Dissociated components of executive control in acute hypobaric hypoxia. Aerosp Med Hu Perform. 2017; 88(12):1081-1087.

I. Discovery of a novel series of CXCR3 antagonists. Multiparametric optimization of N,N-disubstituted benzylamines.

N,N-Disubstituted benzylamine derivatives have been identified as CXCR3 antagonists. Compounds were optimized to improve affinity and selectivity, to increase metabolic stability in human and mouse liver microsomes, to increase Caco-2 permeability. Optimization was supported by monitoring physico-chemical properties using both experimental and computational means. Several compounds with double-digit nanomolar CXCR3 affinity, favorable selectivity, microsomal stability, Caco-2 permeability and human hepatocyte clearance have been identified.

II. Discovery of a novel series of CXCR3 antagonists with a beta amino acid core.

A new series of beta amino acids, which act as CXCR3 antagonists, has been identified. The formerly optimized N,N-disubstituted benzylamine derivatives with carboxylic acid function on the N-atom was used as starting point and compounds with carboxyl function not attached to the N-atom were investigated. Affinity, metabolic stability in human and mouse liver microsomes and Caco-2 permeability were optimized. Compounds with double-digit nanomolar CXCR3 affinity, favourable microsomal stability and Caco-2 permeability have been identified.

Extreme Environment Effects on Cognitive Functions: A Longitudinal Study in High Altitude in Antarctica.

This paper focuses on the impact of long-term Antarctic conditions on cognitive processes. Behavioral responses and event-related potentials were recorded during an auditory distraction task and an attention network paradigm. Participants were members of the over-wintering crew at Concordia Antarctic Research Station. Due to the reduced partial pressure of oxygen this environment caused moderate hypoxia. Beyond the hypoxia, the fluctuation of sunshine duration, isolation and confinement were the main stress factors of this environment. We compared 6 measurement periods completed during the campaign. Behavioral responses and N1/MMN (mismatch negativity), N1, N2, P3, RON (reorientation negativity) event-related potential components have been analyzed. Reaction time decreased in both tasks in response to repeated testing during the course of mission. The alerting effect increased, the inhibition effect decreased and the orienting effect did not change in the ANT task. Contrary to our expectations the N2, P3, RON components related to the attentional functions did not show any significant changes. Changes attributable to early stages of information processing were observed in the ANT task (N1 component) but not in the distraction task (N1/MMN). The reaction time decrements and the N1 amplitude reduction in ANT task could be attributed to sustained effect of practice. We conclude that the Antarctic conditions had no negative impacts on cognitive activity despite the presence of numerous stressors.

Investigation of the antibacterial effects of silver-modified TiO2 and ZnO plasmonic photocatalysts embedded in polymer thin films.

Nanosilver-modified TiO2 and ZnO photocatalysts were studied against methicillin-resistant Staphylococcus aureus on the surface and against naturally occurring airborne microorganisms. The photocatalysts/polymer nanohybrid films were prepared by spray coating technique on the surface of glass plates and on the inner surface of the reactive light source. The photoreactive surfaces were activated with visible light emitting LED light at λ = 405 nm. The optical properties of the prepared photocatalyst/polymer nanohybrid films were characterized by diffuse reflectance measurements. The photocatalytic properties were verified with the degradation of ethanol by gas chromatography measurements. The destruction of the bacterial cell wall component was examined with transmission electron microscope. The antibacterial effect of the photocatalyst/polymer nanohybrid films was tested with different methods and with the associated standard ISO 27447:2009. With the photoreactive coatings, an extensive disinfectant film was developed and successfully prepared. The cell wall component of S. aureus was degraded after 1 h of illumination. The antibacterial effect of the nanohybrid films has been proven by measuring the decrease of the number of methicillin-resistant S. aureus on the surface and in the air as the function of illumination time. The photocatalyst/polymer nanohybrid films could inactivate 99.9 % of the investigated bacteria on different thin films after 2 h of illumination with visible light source. The reactive light source with the inner-coated photocatalyst could kill 96 % of naturally occurring airborne microorganisms after 48 h of visible light illumination in indoor air sample. The TEM results and the microbiological measurements were completed with toxicity tests carried out with Vibrio fischeri bioluminescence bacterium.

Oblique effect in visual mismatch negativity.

We investigated whether visual orientation anisotropies (known as oblique effect) exist in non-attended visual changes using event-related potentials (ERP). We recorded visual mismatch negativity (vMMN) which signals violation of sequential regularities. In the visual periphery unattended, task-irrelevant Gábor patches were displayed in an oddball sequence while subjects performed a tracking task in the central field. A moderate change (50°) in the orientation of stimuli revealed no consistent change-related components. However, we found orientation-related differences around 170 ms in occipito-temporal areas in the amplitude of the ERPs evoked by standard stimuli. In a supplementary experiment we determined the amount of orientation difference that is needed for change detection in an active, attended paradigm. Results exhibited the classical oblique effect; subjects detected 10° deviations from cardinal directions, while threshold from oblique directions was 17°. These results provide evidence that perception of change could be accomplished at significantly smaller thresholds, than what elicits vMMN. In Experiment 2 we increased the orientation change to 90°. Deviant-minus-standard difference was negative in occipito-parietal areas, between 120 and 200 ms after stimulus onset. VMMNs to changes from cardinal angles were larger and more sustained than vMMNs evoked by changes from oblique angles. Changes from cardinal orientations represent a more detectable signal for the automatic change detection system than changes from oblique angles, thus increased vMMN to these "larger" deviances might be considered a variant of the magnitude of deviance effect rarely observed in vMMN studies.

Stimulus complexity effects on the event-related potentials to task-irrelevant stimuli.

The effects of irrelevant stimuli complexity on event-related potentials were investigated in 3 conditions using both auditory and visual oddball tasks. In Conditions 1 and 2, simple standard and target stimuli were presented in series with complex, identical (Condition 1) or variable (Condition 2), task-irrelevant stimuli. In Condition 3, complex standards and targets were presented with simple, identical, task-irrelevant stimuli. In Conditions 1 and 2, but not Condition 3, the irrelevant stimuli elicited the P3a component in both auditory and visual modalities and the N2b component in the visual modality. While we found that variable, irrelevant stimuli evoked larger P3a in the auditory modality compared with identical irrelevant stimuli, we observed the opposite effect in the visual modality. These results suggest that stimuli rareness and irrelevance are not sufficient for eliciting P3a. This component is only elicited by irrelevant stimuli that are at least as complex as the task-related stimuli.

Newborn infants process pitch intervals.

OBJECTIVE: We investigated whether the auditory system of newborn babies extracts the constancy of a pitch interval from exemplars varying in absolute pitch. METHODS: Event-related brain potentials (ERP) were recorded from healthy newborn infants in an oddball paradigm consisting of frequent standard and infrequent deviant tone pairs. Tone pairs varied in absolute frequency. Standard and deviant pairs differed in the amount of pitch difference within the pairs, but not in the direction of pitch change. RESULTS: Deviant tone pairs elicited a discriminative ERP response. CONCLUSIONS: This result suggests that the neonate auditory system represents pitch intervals similarly to adults. SIGNIFICANCE: Adult-like processing of pitch intervals allows newborn infants to learn music, speech prosody, and to process various important auditory cues based on spectral acoustic features.