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Proanthocyanidins (PAs) are known as flavor precursors of a chocolate. In the course post-harvest processes (fermentation and drying), PAs impart astringency and bitterness to many cacao bean genotypes. The goal of this work was therefore to see if there was a relationship between expression level of Tc-MYBPAgene and PAs content in cacao bean (fermentation and drying). Five cacao hybrid genotypes and one commercial cocoa were used to assess physicochemical parameters (pH, fermentation index and cut-testscore). Later, spectrophotometric method was used to assess PAs content, while epicatechin and procyanidin C1 were identified in cacao beans using Ultra Performance Liquid Chromatography-Diode array detector- Electrospry Ionization –Mass spectrometry (UPLC-DAD-ESI(+)-MS). Tc-MYBPAgene expression [by semi-quantitative Reverse Transcription and Polymerase Chain Reaction (semi qRT-PCR)] in each genotype was evaluated. Following cut-test, commercial cocoa cotyledon color is shown weak success fermentation (14% of brown beans) and is positively correlated at small PA accumulation level (9.71 ± 1.27 mg CEq/g defatted cacao powder) (P˂0.05). Four genotypes SCA12×ICS40, ICS40×SCA12, ICS40×UPA134 and SNK16×T60/887 have exhibited more than 60% fully brown colored beans formed during fermentation and drying and vary directly with highest PAs content in cacao (P˂0.05). (-)-epicatechin (in all genotypes) and procyanidin C1 (only SNK10×IMC67 and SNK16×T60/887) were identified in genotype beans. After post-harvest processes, cacao beans from the SCA12×ICS40 (1.75) and ICS40×UPA134 (1.79) genotypes had the highest levels of Tc-MYBPAgene expression. However, weak positive correlation (r= 0.311) was displayed between expression of Tc-MYBPAgene and PAs content of the cacao hybrids studied. Thus, the more preferred indicators for identifying well-fermented cacao beans following post-harvest operations are physicochemical parameters such as pH, cut-test and IF. These cacao beans are often rich in polyphenols such PA. Moreover, our findings prove that the biosynthesis of PA in cacao seeds cannot be regulated by the Tc-MYBPAgene alone. This suggests that expression of the Tc-MYBPAgene that codes for an essential enzyme involved in PAs biosynthesis.

Unconventional quasiparticles emerging in the fractional quantum Hall regime1,2present the challenge of observing their exotic properties unambiguously. Although the fractional charge of quasiparticles has been demonstrated for nearly three decades3–5, the first convincing evidence of their anyonic quantum statistics has only recently been obtained6,7and, so far, the so-called scaling dimension that determines the propagation dynamics of the quasiparticles remains elusive. In particular, although the nonlinearity of the tunnelling quasiparticle current should reveal their scaling dimension, the measurements fail to match theory, arguably because this observable is not robust to non-universal complications8–12. Here we expose the scaling dimension from the thermal noise to shot noise crossover and observe an agreement with expectations. Measurements are fitted to the predicted finite-temperature expression involving both the scaling dimension of the quasiparticles and their charge12,13, in contrast to previous charge investigations focusing on the high-bias shot-noise regime14. A systematic analysis, repeated on several constrictions and experimental conditions, consistently matches the theoretical scaling dimensions for the fractional quasiparticles emerging at filling factors ν= 1/3, 2/5 and 2/3. This establishes a central property of fractional quantum Hall anyons and demonstrates a powerful and complementary window into exotic quasiparticles.

We present a compact 3D diffractive microscope that can be inserted directly in a cell incubator for long-term observation of developing organisms. Our setup is particularly simple and robust, since it does not include any moving parts and is compatible with commercial cell culture containers. It has been designed to image large specimens (>100×100×100µm^3) with subcellular resolution. The sample’s optical properties [refractive index (RI) and absorption] are reconstructed in 3D from intensity-only images recorded with different illumination angles produced by an LED array. The reconstruction is performed using the beam propagation method embedded inside a deep-learning network where the layers encode the optical properties of the object. This deep neural network is trained for a given multiangle intensity acquisition. After training, the weights of the neural network deliver the 3D distribution of the optical properties of the sample. The effect of spherical aberrations due to the sample holder/air interfaces are taken into account in the forward model. Using this approach, we performed time-lapse 3D imaging of preimplantation mouse embryos over six days. Images of embryos from a single cell (low-scattering regime) to the blastocyst stage (highly scattering regime) were successfully reconstructed. Due to its subcellular resolution, our system can provide quantitative information on the embryos’ development and viability. Hence, this technology opens what we believe to be novel opportunities for 3D label-free live-cell imaging of whole embryos or organoids over long observation times.

BackgroundOligoasthenoteratozoospermia is a typical feature of sperm malformations leading to male infertility. Only a few genes have been clearly identified as pathogenic genes of oligoasthenoteratozoospermia.Methods and resultsHere, we identified a homozygous frameshift variant (c.731dup, p.Asn244Lysfs*3) in CCDC34, which is preferentially expressed in the human testis, using whole-exome sequencing in a cohort of 100 Chinese men with multiple morphological abnormalities of the sperm flagella (MMAF). In an additional cohort of 167 MMAF-affected men from North Africa, Iran and France, we identified a second subject harbouring a homozygous CCDC34frameshift variant (c.799_817del, p.Glu267Lysfs*72). Both affected men presented a typical MMAF phenotype with an abnormally low sperm concentration (ie, oligoasthenoteratozoospermia). Transmission electron microscopy analysis of the sperm flagella affected by CCDC34deficiency further revealed dramatic disorganisation of the axoneme. Immunofluorescence assays of the spermatozoa showed that CCDC34deficiency resulted in almost absent staining of CCDC34 and intraflagellar transport-B complex-associated proteins (such as IFT20 and IFT52). Furthermore, we generated a mouse Ccdc34frameshift mutant using CRISPR-Cas9 technology. Ccdc34-mutated (Ccdc34mut/mut) male mice were sterile and presented oligoasthenoteratozoospermia with typical MMAF anomalies. Intracytoplasmic sperm injection has good pregnancy outcomes in both humans and mice.ConclusionsOur findings support that CCDC34is crucial to the formation of sperm flagella and that biallelic deleterious mutations in CCDC34/Ccdc34cause male infertility with oligoasthenoteratozoospermia in humans and mice.

Background: Noninvasive instruments such as plasma D-dimer measurement (DD) and lower-limb compression ultrasonogaphy (US) are being increasingly advocated to reduce the number of necessary angiograms in patients having suspected pulmonary embolism (PE) and a nondiagnostic lung scan. We therefore designed a decision analysis model (1) to evaluate the cost-effectiveness of combining these noninvasive diagnostic aids with lung scan and angiography in the diagnosis of PE and (2) to determine the optimal sequence and combination of tests taking into account the clinical probability of PE. Methods: We performed a cost-effectiveness analysis based on literature data, including data from a management study in our institution. Six diagnostic strategies were compared with the reference, ie, lung scan followed when nondiagnostic (low or intermediate probability) by angiography. In all strategies, PE was ruled out by a normal or near-normal scan, a negative DD (plasma level below 500 [Mu]g/L), or a negative angiogram. Pulmonary embolism was diagnosed and anticoagulant treatment was undertaken in the presence of a high-probability lung scan, deep vein thrombosis showed by US, or a positive angiogram. In case of a nondiagnostic scan (low or intermediate probability), patients could be either treated or not treated, or undergo other tests, according to the selected strategy. Results: Under baseline conditions (prevalence of PE, 35%), strategies combining DD and US with lung scan, angiography being done only in case of an inconclusive noninvasive workup (DD level [is greater than] 500 [Mu]g/L, normal US, and nondiagnostic lung scan), were most cost-effective. This approach yielded a 9% incremental cost reduction and a 37% to 47% decrease in the number of necessary angiograms compared with the reference strategy (scan[+ or -]angiography). For patients with a low clinical probability of PE ([is less than or equal to] 20%), withholding treatment from those with a low-probability lung scan without performing an angiogram proved safe and highly cost-effective (30% cost reduction), provided US showed no deep vein thrombosis. Conclusion: The DD test and US are cost-effective in the diagnostic workup of PE, whether performed after or before lung scan, thus allowing centers devoid of lung scanning and/or angiography facilities to screen patients with suspected PE and avoid costly referrals. In patients with a low clinical probability, a low-probability lung scan, and a normal US, treatment may be withheld without resorting to angiography.

•Chronic pain (CP) was associated with cognitive impairment (CI) in cross-sectional studies.•The potential role of CI on CP occurrence remains debated.•The association between CI and CP occurrence was examined prospectively.•Lower cognitive inhibition was associated with a higher risk of developing CP.

L’objectif de cette étude est d’analyser de manière prospective l’association entre les caractéristiques de sommeil subjectives et basées sur la polysomnographie (PSG) et l’incidence de trouble dépressif majeur (TDM).

There are no studies which have compared the risk of severe COVID‐19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID‐19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n= 306) and a single‐center cohort of nontransplant patients (n= 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID‐19 or mortality. Severe COVID‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe COVID‐19 did not differ between KTR and nontransplant patients; however, 30‐day COVID‐19‐related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p= .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe COVID‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID‐19‐related mortality compared to nontransplant hospitalized patients. The increased mortality risk observed for hospitalized kidney transplant recipients compared to matched nontransplant patients is primarily driven by altered kidney function.

Ces recommandations communes de l’Association Française d’Urologie (AFU) et de la Société d’Andrologie de Langue Française (SALF) ont pour objectif de fournir des directives pratiques à la communauté urologique et andrologique Française concernant l’évaluation des hommes infertiles.

Atomic-scale incorporation of CuAlSe2inclusions within the Cu2Se matrix, achieved through a solid-state transformation of CuSe2template precursor using elemental Cu and Al, enables a unique temperature-dependent dynamic doping of the Cu2Se matrix. The CuAlSe2inclusions, due to their ability to accommodate a large fraction of excess metal atoms within their crystal lattice, serve as a “reservoir” for Cu ions diffusing away from the Cu2Se matrix. Such unidirectional diffusion of Cu ions from the Cu2Se matrix to the CuAlSe2inclusion leads to the formation, near the CuAlSe2/Cu2Se interface, of a high density of Cu-deficient β-Cu2−δSe nanoparticles within the α-Cu2Se matrix and the formation of Cu-rich Cu1+yAlSe2nanoparticles with the CuAlSe2inclusions. This gives rise to a large enhancement in carrier concentration and electrical conductivity at elevated temperatures. Furthermore, the nanostructuring near the CuAlSe2/Cu2Se interface, as well as the extensive atomic disorder in the Cu2Se and CuAlSe2phases, significantly increases phonon scattering, leading to suppressed lattice thermal conductivity. Consequently, a significant improvement in ZT is observed for selected Cu2Se/CuAlSe2composites. This work demonstrates the use of in situ-formed interactive secondary phases in a semiconducting matrix as an elegant alternative approach for further improvement of the performance of leading thermoelectric materials.

Designing crystalline solids in which intrinsically and extremely low lattice thermal conductivity mainly arises from their unique bonding nature rather than structure complexity and/or atomic disorder could promote thermal energy manipulation and utilization for applications ranging from thermoelectric energy conversion to thermal barrier coatings. Here, we report an extremely low lattice thermal conductivity of ∼0.34 W m–1K–1at 300 K in the new complex sulfosalt MnPb16Sb14S38. We attribute the ultralow lattice thermal conductivity to a synergistic combination of scattering mechanisms involving (1) strong bond anharmonicity in various structural building units, owing to the presence of stereoactive lone-electron-pair (LEP) micelles and (2) phonon scattering at the interfaces between building units of increasing size and complexity. Remarkably, low-temperature heat capacity measurement revealed a Cpvalue of 0.206 J g–1K–1at T> 300 K, which is 22% lower than the Dulong–Petit value (0.274 J g–1K–1). Further analysis of the Cpdata and sound velocity (ν= 1834 m s–1) measurement yielded Debye temperature values of 161 and 187 K, respectively. The resulting Grüneisen parameter, γ = 1.65, further supports strong bond anharmonicity as the dominant mechanism responsible for the observed extremely low lattice thermal conductivity.

Entropy stabilization is a novel materials-design paradigm to realize new compounds with widely tunable properties. However, almost all entropy-stabilized materials so far are either conducting metals or insulating ceramics, with a clear dearth in the semiconducting regime. Here, a new class of the multicationic and -anionic entropy-stabilized chalcogenide alloys based on the (Ge,Sn,Pb)(S,Se,Te) formula are synthesized and characterized experimentally. The configurational entropy from the disorder of both the anion and the cation sublattices reaches a record value of ∼2.2 Rmol–1for the equimolar composition and stabilizes the single-phase solid solution. Theoretical calculations and experiments both show that the synthesized alloys are thermodynamically stable at the growth temperature and kinetically metastable at room temperature, segregating by spinodal decomposition at moderate temperatures. Doping and electronic transport measurements verify that the synthesized materials are ambipolarly dopable semiconductors, which pave the way for the wider adoption of entropy-stabilized chalcogenide alloys in functional applications.

Crystal polymorphism selection during synthesis is extremely challenging. However, promoting the formation of a specific metastable polymorph enables modulation of the functional properties of phase-change materials through alteration of the relative abundance of various polymorphs. Here, we demonstrate the stabilization of the superionic β-Cu2Se phase under ambient conditions and the direct control over the relative ratio between the α-Cu2Se and β-Cu2Se polymorphs in (x)CuGaSe2/(1–x)Cu2Se composites using CuGaSe2nanoseeds. We found that the small lattice mismatch between β-Cu2Se (cubic) and the abplane of tetragonal CuGaSe2nanoseeds promotes the formation of low-energy coherent CuGaSe2/β-Cu2Se interfaces, leading to preferential stabilization of β-Cu2Se. Astonishingly, the hierarchical microstructure of the resulting composites enables a remarkable decoupling of charge and heat transport, which is manifested by a breakdown of the Wiedemann–Franz law.

Cd-containing polycrystalline Bi0.46Sb1.54Te3samples with precisely controlled phase composition were synthesized by conventional melting-quenching-annealing technique and a melt-spinning method. The pseudo ternary phase diagram for Cd–Bi/Sb–Te in the region near Bi0.46Sb1.54Te3was systematically studied. Cd serves as an acceptor dopant contributing holes, whereas for samples doped with CdTe, the combined effects of the substitution of Sb/Bi with Cd and the formation of Sb/BiTeantisite defects leads to the increase in hole concentration. Moreover, upon doping with Cd, the lattice thermal conductivity decreases significantly owing to the intensified point defect phonon scattering. The sample with Cd content of 0.01 attains the maximum ZTof 1.15 at 425 K. The utilization of melt-spinning method brings about the in situ nanostructured CdTe and grain size refinement, which further reduce the lattice thermal conductivity while preserving excellent electrical performance. As a result, a higher ZTof 1.30 at 425 K is realized with CdTe content x= 0.005.

Objectives: Atopic diseases and adverse childhood experiences are associated with neurodevelopmental disorders including developmental stuttering. This study examined the associations between these factors and lifetime prevalence, age of onset, and persistence of developmental stuttering. Methods: Data from 4874 participants (2264 men and 2610 women) from the PsyCoLaus study were used. Prevalence, age of onset, and persistence of stuttering were investigated through univariate, bivariate, and regression analyses. Results: Regression analyses indicated that hay fever, gender, familial aggregation, and fear of punishment by parents were associated with stuttering onset in childhood with odds ratios (OR) of 2–3. Hay fever was associated with an earlier onset of stuttering (difference of 1.5 years, p= .001). Moreover, early onset of stuttering (OR = 0.8, p= .009) and hay fever (OR = 9.2, p= .002) predicted whether stuttering persisted. Conclusions: This study suggests that immunological imbalances related to atopic diseases such as hay fever and adverse childhood experiences are also related to stuttering. The importance of this link is emphasized by the fact that hay fever is also associated with age of onset and persistence of stuttering.

BackgroundMale infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases.Methods and resultWe conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65homozygous mutations were identified in four unrelated consanguineous families, and CFAP65compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF.ConclusionsOur experimental observations performed on both human subjects and on Cfap65-mutated mice demonstrate that the presence of biallelic mutations in CFAP65causes the MMAF phenotype and impairs sperm motility.

The objective of these clinical practice guidelines was to analyse all of the interventions during pregnancy and childbirth that might prevent obstetric anal sphincter injuries (OASIS) and postnatal pelvic floor symptoms.

Analyser la littérature, les textes réglementaires et les pratiques concernant l’information des femmes dans le domaine de l’accouchement.

AbstractThe Stratospheric Ozone Differential Absorption Lidar (DIAL) located at the Polar Environment Atmospheric Research Laboratory (PEARL) in Eureka, Nunavut (80°N, 86°W) has been a powerful tool for the measurement of stratospheric ozone vertical profiles in the Canadian High Arctic since 1993. The lidar ozone profiles measured during the 2017 Canadian Arctic Atmospheric Chemistry Experiment (ACE) and Optical Spectrograph and InfraRed Imaging System (OSIRIS) Validation Campaign were compared to coincident ozonesonde, ACE-FTS, ACE-MAESTRO and OSIRIS profiles. The results show the lidar overestimates the ozone by ∼10% in the 10 km–20 km altitude range on average in comparison with the ozonesonde. Above 20 km the profiles agree within 10%. The OSIRIS ozone agrees within 10% with DIAL ozone between 15 km and 41 km. A strong stratospheric ozone depletion event was seen on March 3, 2017, during which the ozone concentration dropped below 1012molecules cm–3at the 15.5 km and below 6 × 1012molecules cm–3at 16 km as measured by the ozonesonde and the lidar correspondingly. Laminated structures were observed in the ozonesonde profiles near the polar vortex edge regions. This together with non-optimal temporal and spatial coincidences between the measurements conducted by different instruments can affect validation accuracy.

Ferromagnetic semiconductors (FMSs) featuring a high Curie transition temperature (Tc) and a strong correlation between itinerant carriers and localized magnetic moments are of tremendous importance for the development of practical spintronic devices. The realization of such materials hinges on the ability to generate and manipulate a high density of itinerant spin-polarized carriers and the understanding of their responses to external stimuli. In this study, we demonstrate the ability to tune magnetic ordering in the p-type FMS FeSb2–xSnxSe4(0 ≤ x≤ 0.20) through carrier density engineering. We found that the substitution of Sb by Sn FeSb2–xSnxSe4increases the ordering of metal atoms within the selenium crystal lattice, leading to a large separation between magnetic centers. This results in a decrease in the Tcfrom 450 K for samples with x≤ 0.05 to 325 K for samples with 0.05 < x≤ 0.2. In addition, charge disproportionation arising from the substitution of Sb3+by Sn2+triggers the partial oxidation of Sb3+to Sb5+, which is accompanied by the generation of both electrons and holes. This leads to a drastic decrease in the electrical resistivity and thermopower simultaneously with a large increase in the magnetic susceptibility and saturation magnetization upon increasing Sn content. The observed bipolar doping induces a very interesting temperature-induced quantum electronic transition (Lifshitz transition), which is manifested by the presence of an anomalous peak in the resistivity curve simultaneously with a reversal of the sign of a majority of the charge carriers from hole-like to electron-like at the temperature of maximum resistivity. This study suggests that while there is a strong correlation between the overall magnetic moment and free carrier spin in FeSb2–xSnxSe4FMSs, the magnitude of the Curie temperature strongly depends on the spatial separation between localized magnetic centers rather than the concentration of magnetic atoms or the density of itinerant carriers.

Understanding the nature and origin of high-temperature ferromagnetic-like ordering in complex semiconducting transition metal selenides, such as FeBi2Se4, is extremely important and could shed light on novel approaches to develop high-Tcferromagnetism in traditional semiconductors. Here, we report on the effect of partial substitution of Fe by Sn on the distribution of magnetic centers within the Fe1–xSnxBi2Se4crystal lattice and its impact on the electronic and magnetic properties. Several compositions of the Fe1–xSnxBi2Se4(0.1 ≤ x≤ 0.5) solid solution were synthesized by combining high-purity elements in the respective stoichiometric ratios. Powder X-ray diffraction suggests that the synthesized phases are isostructural with the parent compound, FeBi2Se4, despite the large difference in the ionic radii of Fe2+and Sn2+in octahedral coordination. Single-crystal X-ray diffraction reveals increased ordering in the distribution of Fe2+, Sn2+, and Bi3+atoms in various metal sites within the crystal structure, with full atomic ordering reached for the Fe0.5Sn0.5Bi2Se4(x= 0.5) composition. High-temperature direct current (dc) magnetic susceptibility measurements reveal that all Fe1–xSnxBi2Se4samples remain ferromagnetic over a wide temperature range and the Curie transition temperature, Tc, decreases from ∼450 K for compositions with x≤ 0.15 to 325 K for compositions with high Sn content. The observed drop in Tcis ascribed to an increased separation between the magnetic centers for compositions with x> 0.15. Hall effect measurements confirm the n-type semiconducting nature of all compounds. Interestingly, the carrier density of Fe1–xSnxBi2Se4samples gradually decreases with decreasing temperature down to 150 K, below which a remarkable transition from semiconducting to metallic behavior is observed for compositions with x≥ 0.25.

DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2’-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. The deposition of m6dA is associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with extinction-induced gene expression. The accumulation of m6dA is associated with transcriptional activation at the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnfexon IV messenger RNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as an epigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

Animals strategically scan the environment to form an accurate perception of their surroundings. Here we investigated the neuronal representations that mediate this behavior. Ca2+imaging and selective optogenetic manipulation during an active sensing task reveals that layer 5 pyramidal neurons in the vibrissae cortex produce a diverse and distributed representation that is required for mice to adapt their whisking motor strategy to changing sensory cues. The optogenetic perturbation degraded single-neuron selectivity and network population encoding through a selective inhibition of active dendritic integration. Together the data indicate that active dendritic integration in pyramidal neurons produces a nonlinearly mixed network representation of joint sensorimotor parameters that is used to transform sensory information into motor commands during adaptive behavior. The prevalence of the layer 5 cortical circuit motif suggests that this is a general circuit computation.

Presents a speech by Pierre F. Dobbelmann, executive director of the Netherlands Foreign Investment Agency, delivered before the World Council of Pittsburgh in Pittsburgh, Pennsylvania on May 19, 1987. Focus of Dutch economy on foreign trade; Roots of protectionism in the U.S.; Examples of perils of protectionism.

Relationship to macroangiopathy, nephropathy, and insulin resistance OBJECTIVE -- The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients [...]

Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery. A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up. PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/β blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications. PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

Supplemental digital content is available in the text.

Single-phase polycrystalline powders of Sr1–xSbxHfSe3(x= 0, 0.005, 0.01), a new member of the chalcogenide perovskites, were synthesized using a combination of high temperature solid-state reaction and mechanical alloying approaches. Structural analysis using single-crystal as well as powder X-ray diffraction revealed that the synthesized materials are isostructural with SrZrSe3, crystallizing in the orthorhombic space group Pnma(#62) with lattice parameters a= 8.901(2) Å; b= 3.943(1) Å; c= 14.480(3) Å; and Z= 4 for the x= 0 composition. Thermal conductivity data of SrHfSe3revealed low values ranging from 0.9 to 1.3 W m–1K–1from 300 to 700 K, which is further lowered to 0.77 W m–1K–1by doping with 1 mol % Sb for Sr. Electronic property measurements indicate that the compound is quite insulating with an electrical conductivity of 2.9 S/cm at 873 K, which was improved to 6.7 S/cm by 0.5 mol % Sb doping. Thermopower data revealed that SrHfSe3is a p-type semiconductor with thermopower values reaching a maximum of 287 μV/K at 873 K for the 1.0 mol % Sb sample. The optical band gap of Sr1–xSbxHfSe3samples, as determined by density functional theory calculations and the diffuse reflectance method, is ∼1.00 eV and increases with Sb concentration to 1.15 eV. Careful analysis of the partial densities of states (PDOS) indicates that the band gap in SrHfSe3is essentially determined by the Se-4p and Hf-5d orbitals with little to no contribution from Sr atoms. Typically, band edges of p- and d-character are a good indication of potentially strong absorption coefficient due to the high density of states of the localized p and d orbitals. This points to potential application of SrHfSe3as absorbing layer in photovoltaic devices.

In nanoscale electronic circuits, controlling the flow of heat is essential. A demonstration of a heat Coulomb blockade arising from thermal many-body effects shows that thermal transport follows distinct rules in the quantum regime.

Bioassay-guided fractionation of culture extracts of Serratia plymuthicastrain MF371-2 resulted in the isolation of two new antibacterial compounds with potent activity against Gram-positive bacteria, including Staphylococcus aureusLMG 15975 (MRSA). A spectroscopic investigation, in combination with synthesis, enabled the characterization of the compounds as 3-butyryl-4-hydroxy-6-heptyl-5,6-dihydro-2H-pyran-2-one (plymuthipyranone A, 1) and 3-butyryl-4-hydroxy-6-nonyl-5,6-dihydro-2H-pyran-2-one (plymuthipyranone B, 2). The MIC values for 1and 2against S. aureusLMG 15975 were determined to be 1–2 μg mL–1and 0.8 μg mL–1, respectively. Compound 2was found to have potent activity against many strains of S. aureus, including several mupirocin-resistant strains, other species of Staphylococcus, and vancomycin-resistant enterococci. Compound 2was slightly cytotoxic for human cells, with CC50values between 4.7 and 40 μg mL–1, but the CC50/MIC ratio was ≥10 for many tested combinations of human cells and bacteria, suggesting its possible use as an antibacterial agent. Several analogues were synthesized with different alkyl groups in the 3- and 6-positions (6–13), and their biological properties were evaluated. It was concluded that the activity of the compounds increased with the lengths of the alkyl and acyl substituents.

Over the last 3–4 decades, solid-state chemistry has emerged as the forefront of materials design and development. The field has revolutionized into a multidisciplinary subject and matured with a scope of new synthetic strategies, new challenges, and opportunities. Understanding the structure is very crucial in the design of appropriate materials for desired applications. Professor Mercouri G. Kanatzidis has encountered both challenges and opportunities during the course of the discovery of many novel materials. Throughout his scientific career, Mercouri and his group discovered several inorganic compounds and pioneered structure–property relationships. We, a few Ph.D. and postdoctoral students, celebrate his 60th birthday by providing a Viewpoint summarizing his contributions to inorganic solid-state chemistry. The topics discussed here are of significant interest to various scientific communities ranging from condensed matter to green energy production.

We integrate data-driven ocean modeling with the stochastic Dynamically Orthogonal (DO) level-set optimization methodology to compute and study energy-optimal paths, speeds, and headings for ocean vehicles in the Middle-Atlantic Bight (MAB) region. We hindcast the energy-optimal paths from among exact time-optimal paths for the period 28 August 2006 to 9 September 2006. To do so, we first obtain a data-assimilative multiscale reanalysis, combining ocean observations with implicit two-way nested multiresolution primitive-equation simulations of the tidal-to-mesoscale dynamics in the region. Second, we solve the reduced-order stochastic DO level-set partial differential equations (PDEs) to compute the joint probability of minimum arrival time, vehicle-speed time series, and total energy utilized. Third, for each arrival time, we select the vehicle-speed time series that minimize the total energy utilization from the marginal probability of vehicle-speed and total energy. The corresponding energy-optimal path and headings are obtained through the exact particle-backtracking equation. Theoretically, the present methodology is PDE-based and provides fundamental energy-optimal predictions without heuristics. Computationally, it is 3–4 orders of magnitude faster than direct Monte Carlo methods. For the missions considered, we analyze the effects of the regional tidal currents, strong wind events, coastal jets, shelfbreak front, and other local circulations on the energy-optimal paths. Results showcase the opportunities for vehicles that intelligently utilize the ocean environment to minimize energy usage, rigorously integrating ocean forecasting with optimal control of autonomous vehicles. Fundamental energy-optimal path planning, rigorously utilizing realistic multiscale ocean forecastsUsing stochastic optimization showcased energy-optimal paths in data-assimilative simulationsAnalyzed effects of tides, wind events, jets, shelfbreak front, and local circulations on the paths

An overview of labor based only on epidemiological data cannot identify or explain the mechanisms involved in childbirth. Data about the position that women should take in giving birth are discordant. None of the studies of birth positions adequately define or describe them or their biomechanical impact (pelvic orientation, position of the back). The measurement of the effect of one position relative to that of another requires precise definitions of each position and of their maternal biomechanical consequences, as well as safe measurement methods.

Pb6Bi2Se9, the selenium analogue of heyrovsyite, crystallizes in the orthorhombic space group Cmcm(#63) with a= 4.257(1) Å, b= 14.105(3) Å, and c= 32.412(7) Å at 300 K. Its crystal structure consists of two NaCl-type layers, A and B, with equal thickness, N1= N2= 7, where Nis the number of edge-sharing [Pb/Bi]Se6octahedra along the central diagonal. In the crystal structure, adjacent layers are arranged along the c-axis such that bridging bicapped trigonal prisms, PbSe8, are located on a pseudomirror plane parallel to (001). Therefore, Pb6Bi2Se9corresponds to a 7,7L member of the lillianite homologous series. Electronic transport measurements indicate that the compound is a heavily doped narrow band gap n-type semiconductor, with electrical conductivity and thermopower values of 350 S/cm and −53 μV/K at 300 K. Interestingly, the compound exhibits a moderately low thermal conductivity, ∼1.1 W/mK, in the whole temperature range, owing to its complex crystal structure, which enables strong phonon scattering at the twin boundaries between adjacent NaCl-type layers A and B. The dimensionless figure of merit, ZT, increases with temperature to 0.25 at 673 K.

BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) represent a significant healthcare burden since it is the primary cause of chronic kidney in children. CNVs represent a recurrent molecular cause of CAKUT but the culprit gene remains often elusive. Our study aimed to define the gene responsible for CAKUT in patients with an 1q23.3q24.1 microdeletion.MethodsWe describe eight patients presenting with CAKUT carrying an 1q23.3q24.1 microdeletion as identified by chromosomal microarray analysis (CMA). Clinical features were collected, especially the renal and urinary tract phenotype, and extrarenal features. We characterised PBX1expression and localisation in fetal and adult kidneys using quantitative RT-PCR and immunohistochemistry.ResultsWe defined a 276-kb minimal common region (MCR) that only overlaps with the PBX1gene. All eight patients presented with syndromic CAKUT. CAKUT were mostly bilateral renal hypoplasia (75%). The most frequent extrarenal symptoms were developmental delay and ear malformations. We demonstrate that PBX1is strongly expressed in fetal kidneys and brain and expression levels decreased in adult samples. In control fetal kidneys, PBX1 was localised in nuclei of medullary, interstitial and mesenchymal cells, whereas it was present in endothelial cells in adult kidneys.ConclusionsOur results indicate that PBX1haploinsufficiency leads to syndromic CAKUT as supported by the Pbx1-null mice model. Correct PBX1 dosage appears to be critical for normal nephrogenesis and seems important for brain development in humans. CMA should be recommended in cases of fetal renal anomalies to improve genetic counselling and pregnancy management.

Certaines plaintes concernant le sommeil font partie des critères diagnostiques du trouble dépressif majeur (TDM). Peu d’études ont cherché à savoir si les sous-types cliniques de TDM sont reflétés dans les mesures objectives du sommeil de la polysomnographie (PSG). L’objectif de cette étude est de rechercher des associations entre les sous-types mélancoliques, atypiques et non spécifiés de TDM et les caractéristiques objectives du sommeil mesurées par PSG.

•What is the primary question addressed by this study?Are the subtypes of major depressive disorder according to the diagnostic and statistical manual of mental disorders (DSM-IV) specifiers stable in advanced age and what is the influence of mild cognitive impairment on this stability?•What is the main finding of this study?Longitudinal stability into advanced age of the atypical and the combined subtypes but not of the melancholic subtype of major depressive disorder according to the DSM-IV specifiers and absence of the effect of mild cognitive impairment on this stability.•What is the meaning of the finding?Additional support for the validity of the atypical subtype of major depressive disorder according to the DSM-IV specifier in older age.

A device consisting of a metallic island connected to electrodes via tunable semiconductor-based conduction channels is used to explore the evolution of charge quantization in the presence of quantum fluctuations; the measurements reveal a robust scaling of charge quantization as the square root of the residual electron reflection probability across a quantum channel, consistent with theoretical predictions.

Internal tides in the Middle Atlantic Bight region are found to be noticeably influenced by the presence of the shelfbreak front and the Gulf Stream, using a combination of observations, equations, and data‐driven model simulations. To identify the dominant interactions of these waves with subtidal flows, vertical‐mode momentum and energy partial differential equations are derived for small‐amplitude waves in a horizontally and vertically sheared mean flow and in a horizontally and vertically variable density field. First, the energy balances are examined in idealized simulations with mode‐1 internal tides propagating across and along the Gulf Stream. Next, the fully nonlinear dynamics of regional tide‐mean‐flow interactions are simulated with a primitive‐equation model, which incorporates realistic summer‐mesoscale features and atmospheric forcing. The shelfbreak front, which has horizontally variable stratification, decreases topographic internal‐tide generation by about 10% and alters the wavelengths and arrival times of locally generated mode‐1 internal tides on the shelf and in the abyss. The (sub)mesoscale variability at the front and on the shelf, as well as the summer stratification itself, also alter internal‐tide propagation. The Gulf Stream produces anomalous regions of O(20 mW m−2) mode‐1 internal‐tide energy‐flux divergence, which are explained by tide‐mean‐flow terms in the mode‐1 energy balance. Advection explains most tide‐mean‐flow interaction, suggesting that geometric wave theory explains mode‐1 reflection and refraction at the Gulf Stream. Geometric theory predicts that offshore‐propagating mode‐1 internal tides that strike the Gulf Stream at oblique angles (more than thirty degrees from normal) are reflected back to the coastal ocean, preventing their radiation into the central North Atlantic. Simulations of the MAB reveal internal‐tide interactions with the Gulf Stream and shelfbreak frontThe shelfbreak front decreases topographic generation and alters the arrival times of internal tidesTide‐mean‐flow interactions in the Gulf Stream are explained by terms in the mode‐1 momentum/energy balance

Le rôle de la grossesse dans l’apparition des troubles de la statique pelvienne est discuté. Il pourrait y avoir au cours de cette période un lien entre les modifications de laxité ligamentaire et les modifications de la statique pelvienne. Notre objectif était de réaliser une revue non systématique de la littérature concernant les modifications de la statique pelvienne et les modifications de laxité ligamentaire au cours de la grossesse puis du post-partum.