Optimizing Quantum Control Pulses with Gaussian Process Priors: The Spectral Way.

This study presents the Gaussian Process Prior Optimization for Pulse Shaping (GPPOPS) methodology, a novel approach to pulse shaping engineering. Its main objective is to efficiently identify laser pulse shapes that can achieve a desired task encoded in a cost function while being experimentally implementable. The AlH+ molecule was utilized as a test case to find pulse shapes that maximized vibronic transitions. The results demonstrate that optimal pulses can be readily implemented using current laser technology and that their control capabilities can withstand noise. The study emphasizes the benefits of constructing a surrogate approach to the control landscape during the optimization process. This approach is expected to be versatile, efficient and readily implementable in the laboratory. Its demonstrated robustness to noise sets it apart from other numerical pulse shaping engineering methods. By reducing the required experimental labor, this method has the potential to facilitate breakthroughs in quantum engineering.

Toward Nonvolatile Spin-Orbit Devices: Deposition of Ferroelectric Hafnia on Monolayer Graphene/Co/HM Stacks.

While technologically challenging, the integration of ferroelectric thin films with graphene spintronics potentially allows the realization of highly efficient, electrically tunable, nonvolatile memories through control of the interfacial spin-orbit driven interaction occurring at graphene/Co interfaces deposited on heavy metal supports. Here, the integration of ferroelectric Hf0.5Zr0.5O2 on graphene/Co/heavy metal epitaxial stacks is investigated via the implementation of several nucleation methods in atomic layer deposition. By employing in situ Al2O3 as a nucleation layer sandwiched between Hf0.5Zr0.5O2 and graphene, the Hf0.5Zr0.5O2 demonstrates a remanent polarization (2Pr) of 19.2 µC/cm2. Using an ex situ, naturally oxidized sputtered Ta layer for nucleation, we could control 2Pr via the interlayer thickness, reaching maximum values of 28 µC/cm2 with low coercive fields. Magnetic hysteresis measurements taken before and after atomic layer deposition show strong perpendicular magnetic anisotropy, with minimal deviations in the magnetization reversal pathways due to the Hf0.5Zr0.5O2 deposition process, thus pointing to a good preservation of the magnetic stack including single-layer graphene. X-ray diffraction measurements further confirm that the high-quality interfaces demonstrated in the stack remain unperturbed by the ferroelectric deposition and anneal. The proposed graphene-based ferroelectric/magnetic structures offer the strong advantages of ferroelectricity and ferromagnetism at room temperature, enabling the development of novel magneto-electric and nonvolatile in-memory spin-orbit logic architectures with low power switching.

Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms.

Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. We have summarized associations of signs and symptoms in 339 inherited metabolic diseases presenting with GI symptoms. Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (37%) followed by intestinal problems (30%), vomiting (22%), stomach and pancreas involvement (8% each), and esophagus involvement (4%). This represents the eleventh of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnoses according to system involvement.

High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La0.67Sr0.33MnO3 for Biomedical Applications.

We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La0.67Sr0.33MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.

Intrinsic Mixed Bloch-Néel Character and Chirality of Skyrmions in Asymmetric Epitaxial Trilayers.

Recent advances in the stabilization and manipulation of chiral magnetization configurations in systems consisting of alternating atomic layers of ferromagnetic and nonmagnetic materials hold promise for innovation in spintronics technology. The low dimensionality of the systems promotes spin orbit driven interfacial effects like antisymmetric Dzyaloshinskii-Moriya interactions (DMI) and surface magnetic anisotropy, whose relative strengths may be tuned to achieve stable nanometer sized magnetic objects with fixed chirality. While in most of the cases this is obtained by engineering complex multilayers stacks in which interlayer dipolar fields become important, we consider here a simple epitaxial trilayer in which a ferromagnet, with variable thickness, is embedded between a heavy metal and graphene. The latter enhances the perpendicular magnetic anisotropy of the system, promotes a Rashba-type DMI, and can sustain very long spin diffusion lengths. We use a layer-resolved micromagnetic model to describe the magnetization textures and their chirality. Our results demonstrate that for Co thicknesses larger than 3.6 nm, a skyrmion having an intrinsic mixed Bloch-Néel character is stabilized in the entire (single) Co layer.

Complex patterns of inheritance, including synergistic heterozygosity, in inborn errors of metabolism: Implications for precision medicine driven diagnosis and treatment.

Inborn errors of metabolism have traditionally been viewed as the quintessential single gene disorders; defects in one gene leads to loss of activity of one enzyme causing a metabolic imbalance and clinical disease. However, reality has never been quite that simple, and the classic "one gene-one enzyme" paradigm has been upended in many ways. Multiple gene defects can lead to the same biochemical phenotype, often with different clinical symptoms. Additionally, different mutations in the same gene can cause variable phenotypes, often most dramatic when a disease can be identified by pre-symptomatic screening. Moreover, response to therapy is not homogeneous across diseases and specific mutations. Perhaps the biggest deviation from traditional monogenic inheritance is in the setting of synergistic heterozygosity, a multigenic inheritance pattern in which mutations in multiple genes in a metabolic pathway lead to sufficient disruption of flux through the pathway, mimicking a monogenic disorder caused by homozygous defects in one gene in that pathway. In addition, widespread adoption of whole exome and whole genome sequencing in medical genetics has led to the realization that individual patients with apparently hybrid phenotypes can have mutations in more than one gene, leading to a mixed genetic disorder. Each of these situations point to a need for as much precision as possible in diagnosing metabolic disease, and it is likely to become increasingly critical to drive therapy. This article examines examples in traditional monogenic disorders that illustrates these points and define inborn errors of metabolism as complex genetic traits on the leading edge of precision medicine.

Inborn Errors of Metabolism and the Gastrointestinal Tract.

Inborn errors of metabolism (IEMs) are usually recognized by characteristic neurologic and metabolic manifestations and sometimes by dysmorphism. However, IEMs can present with a wide variety of gastrointestinal manifestations, whether as the primary or a minor clinical symptom. Regardless, gastrointestinal and hepatic manifestations of IEMs are important clinical features that can help identify an underlying defect; these disorders should be taken into consideration as part of a patient's clinical assessment. It is prudent to include metabolic disorders in the differential diagnosis because in some cases, gastrointestinal symptoms may be the only presenting feature in a patient with an underlying IEM.

Unraveling Dzyaloshinskii-Moriya Interaction and Chiral Nature of Graphene/Cobalt Interface.

A major challenge for future spintronics is to develop suitable spin transport channels with long spin lifetime and propagation length. Graphene can meet these requirements, even at room temperature. On the other side, taking advantage of the fast motion of chiral textures, that is, Néel-type domain walls and magnetic skyrmions, can satisfy the demands for high-density data storage, low power consumption, and high processing speed. We have engineered epitaxial structures where an epitaxial ferromagnetic Co layer is sandwiched between an epitaxial Pt(111) buffer grown in turn onto MgO(111) substrates and a graphene layer. We provide evidence of a graphene-induced enhancement of the perpendicular magnetic anisotropy up to 4 nm thick Co films and of the existence of chiral left-handed Néel-type domain walls stabilized by the effective Dzyaloshinskii-Moriya interaction (DMI) in the stack. The experiments show evidence of a sizable DMI at the gr/Co interface, which is described in terms of a conduction electron mediated Rashba-DMI mechanism and points opposite to the spin orbit coupling-induced DMI at the Co/Pt interface. In addition, the presence of graphene results in (i) a surfactant action for the Co growth, producing an intercalated, flat, highly perfect face-centered cubic film, pseudomorphic with Pt and (ii) an efficient protection from oxidation. The magnetic chiral texture is stable at room temperature and grown on insulating substrate. Our findings open new routes to control chiral spin structures using interfacial engineering in graphene-based systems for future spin-orbitronics devices fully integrated on oxide substrates.

Heuristic optimization of analytic laser pulses for vibrational stabilization of ultracold KRb.

We proposed a methodology that allows to maximize the population transfer from a high vibrational state of the a 3Σ+ triplet state to the vibrational ground state of the X 1Σ+ singlet state though the optimization of one pump and one dump laser pulses. The pump pulse is optimized using a fitness function, heuristically improved, that includes the effect of the spin-orbit coupling of the KRb [b-A]-scheme. The dump pulse is optimized to maximize the population transfer to the ground state. We performed a comparison with the case in which the pump and dump pulses are optimized to maximize the population transfer to the ground state employing a genetic algorithm with a single fitness function. The heuristic approach turned out to be 70% more efficient than a quantum optimal control optimization employing a single fitness function. The method proposed provides simple pulses that have an experimental realm.

Laboratory diagnostic approaches in metabolic disorders.

The diagnosis of inborn errors of metabolism (IEM) takes many forms. Due to the implementation and advances in newborn screening (NBS), the diagnosis of many IEM has become relatively easy utilizing laboratory biomarkers. For the majority of IEM, early diagnosis prevents the onset of severe clinical symptoms, thus reducing morbidity and mortality. However, due to molecular, biochemical, and clinical variability of IEM, not all disorders included in NBS programs will be detected and diagnosed by screening alone. This article provides a general overview and simplified guidelines for the diagnosis of IEM in patients with and without an acute metabolic decompensation, with early or late onset of clinical symptoms. The proper use of routine laboratory results in the initial patient assessment is also discussed, which can help guide efficient ordering of specialized laboratory tests to confirm a potential diagnosis and initiate treatment as soon as possible.

Emergence of the Stoner-Wohlfarth astroid in thin films at dynamic regime.

The Stoner-Wohlfarth (SW) model is the simplest model that describes adequately the magnetization reversal of nanoscale systems that are small enough to contain single magnetic domains. However for larger sizes where multi-domain effects are present, e.g., in thin films, this simple macrospin approximation fails and the experimental critical curve, referred as SW astroid, is far from its predictions. Here we show that this discrepancy could vanish also in extended system. We present a detailed angular-dependent study of magnetization reversal dynamics of a thin film with well-defined uniaxial magnetic anisotropy, performed over 9 decades of applied field sweep rate (dH/dt). The angular-dependent properties display a gradual transition from domain wall pinning and motion-like behaviour to a nucleative single-particle one, as dH/dt increases. Remarkably, in the high dynamic regime, where nucleation of reversed domains is the dominant mechanism of the magnetization reversal (nucleative regime), the magnetic properties including the astroid become closer to the ones predicted by SW model. The results also show why the SW model can successfully describe other extended systems that present nucleative regime, even in quasi-static conditions.

Analytical optimal pulse shapes obtained with the aid of genetic algorithms.

We propose a methodology to design optimal pulses for achieving quantum optimal control on molecular systems. Our approach constrains pulse shapes to linear combinations of a fixed number of experimentally relevant pulse functions. Quantum optimal control is obtained by maximizing a multi-target fitness function using genetic algorithms. As a first application of the methodology, we generated an optimal pulse that successfully maximized the yield on a selected dissociation channel of a diatomic molecule. Our pulse is obtained as a linear combination of linearly chirped pulse functions. Data recorded along the evolution of the genetic algorithm contained important information regarding the interplay between radiative and diabatic processes. We performed a principal component analysis on these data to retrieve the most relevant processes along the optimal path. Our proposed methodology could be useful for performing quantum optimal control on more complex systems by employing a wider variety of pulse shape functions.

Fat-containing lesions of the retroperitoneum: radiologic-pathologic correlation.

Retroperitoneal lesions represent a broad, diverse collection of entities; when they contain fat, the differential diagnosis, which ranges from benign to fully malignant lesions, substantially narrows. Lipomas rarely occur in the retroperitoneum; thus, fat-containing lesions in this location should never be dismissed as lipoma. Pelvic lipomatosis is the overgrowth of histologically normal fat in the extraabdominal compartments of the pelvis along the perirectal and perivesicular spaces. Infants and young children develop lipoblastomas rather than liposarcomas, which occur in older patients. Liposarcomas typically occur in patients 50-70 years old and manifest in multiple subtypes, with the most common being well-differentiated liposarcoma. Liposarcomas are histologically and radiologically protean, with no one imaging feature specific across the spectrum of subtypes. Hibernoma is a rare benign soft-tissue tumor composed of brown fat. Because hibernomas contain varied portions of brown and white fat as well as lesser amounts of myxoid material and spindle cells, their imaging features vary considerably. Teratomas are neoplasms that originate in pluripotent cells--benign or malignant germ cells--that give rise to a wide spectrum of mature or immature tissues that are foreign to the location in which they arise and which demonstrate varying amounts of organ formation. Myelolipoma, a benign tumor composed of mature fat and interspersed hematopoietic elements that resemble bone marrow, typically originate in an otherwise normal adrenal gland. Angiomyolipoma is composed of varying admixtures of blood vessels, smooth muscle cells, and adipose tissue; any one or two of these elements may predominate. Although these fat-containing lesions have overlapping radiologic features, use of demographic and clinical data helps refine the diagnostic options and treatment.

The socioeconomic costs of mental illness in Spain.

Mental illness affects a large number of people in the world, seriously impairing their quality of life and resulting in high socioeconomic costs for health care systems and society. Our aim is to estimate the socioeconomic impact of mental illness in Spain for the year 2002, including health care resources, informal care and loss of labour productivity. A prevalence-based approach was used to estimate direct medical costs, direct non-medical costs, and loss of labour productivity. The total costs of mental illness have been estimated at 7,019 million euros. Direct medical costs represented 39.6% of the total costs and 7.3% of total public healthcare expenditure in Spain. Informal care costs represented 17.7% of the total costs. Loss of labour productivity accounted for 42.7% of total costs. In conclusion, the costs of mental illness in Spain make a considerable economic impact from a societal perspective.

The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX.

BACKGROUND/AIMS: The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis. METHODS: Allelic imbalance on chromosome 16 was analyzed in 73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and apoptosis and the interaction between WWOX and JNK inhibition were examined. RESULTS: Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2 had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated proliferation and enhanced apoptosis induced by staurosporine and the JNK inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA targeting WWOX increased proliferation and resistance to SP600129-induced apoptosis. CONCLUSIONS: WWOX induces apoptosis and inhibits human HCC cell growth through a mechanism enhanced by JNK inhibition.

Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma.

UNLABELLED: It has been shown that the heparin-degrading endosulfatase, sulfatase 1 (SULF1), functions as a liver tumor suppressor, but the role of the related sulfatase, sulfatase 2 (SULF2), in liver carcinogenesis remains to be elucidated. We investigated the effect of SULF2 on liver tumorigenesis. Expression of SULF2 was increased in 79 (57%) of 139 hepatocellular carcinomas (HCCs) and 8 (73%) of 11 HCC cell lines. Forced expression of SULF2 increased HCC cell growth and migration, whereas knockdown of SULF2 using short hairpin RNA targeting SULF2 abrogated HCC cell proliferation and migration in vitro. Because SULF1 and SULF2 desulfate heparan sulfate proteoglycans (HSPGs) and the HSPG glypican 3 (GPC3) is up-regulated in HCC, we investigated the effects of SULF2 on GPC3 expression and the association of SULF2 with GPC3. SULF2-mediated cell growth was associated with increased binding of fibroblast growth factor 2 (FGF2), phosphorylation of extracellular signal-regulated kinase and AKT, and expression of GPC3. Knockdown of GPC3 attenuated FGF2 binding in SULF2-expressing HCC cells. The effects of SULF2 on up-regulation of GPC3 and tumor growth were confirmed in nude mouse xenografts. Moreover, HCC patients with increased SULF2 expression in resected HCC tissues had a worse prognosis and a higher rate of recurrence after surgery. CONCLUSION: In contrast to the tumor suppressor effect of SULF1, SULF2 has an oncogenic effect in HCC mediated in part through up-regulation of FGF signaling and GPC3 expression.

Radiologic evaluation of breast disorders related to pregnancy and lactation.

During pregnancy and lactation, the breast can be affected by a variety of specific and unique disorders, including benign disorders closely related to physiologic changes, inflammatory and infectious diseases, juvenile papillomatosis, and benign and malignant tumors. Patients with pregnancy-associated breast carcinoma tend to have more advanced neoplasms at diagnosis and a poorer prognosis due to delayed diagnosis and a more aggressive biologic pattern. Pregnancy-related Burkitt lymphoma characteristically manifests with bilateral and diffuse involvement of the breasts. Fibroadenoma may manifest with growth, infarction, large cysts, prominent ducts, and secretory hyperplasia during pregnancy and lactation. Galactocele is the breast lesion most commonly found during lactation and manifests as either pseudolipoma, a cystic mass with a fat-fluid level, or pseudohamartoma. Tumors and diseases affecting the breasts during pregnancy and lactation are basically the same as those observed in nonpregnant women but may have a different appearance. The sensitivity of mammography in pregnant and lactating women is decreased due to increased parenchymal density. Instead, ultrasonography is the most appropriate radiologic method for evaluating breast masses in this setting and is particularly useful in the diagnosis and treatment of abscesses. Knowledge of the unique entities that are specifically related to pregnancy and lactation and of their radiologic-pathologic appearances can help the radiologist make the correct diagnosis.

Viscoelasticity of mono- and polydisperse inverse ferrofluids.

We report on measurements of a magnetorheological model fluid created by dispersing nonmagnetic microparticles of polystyrene in a commercial ferrofluid. The linear viscoelastic properties as a function of magnetic field strength, particle size, and particle size distribution are studied by oscillatory measurements. We compare the results with a magnetostatic theory proposed by De Gans et al. [Phys. Rev. E 60, 4518 (1999)] for the case of gap spanning chains of particles. We observe these chain structures via a long distance microscope. For monodisperse particles we find good agreement of the measured storage modulus with theory, even for an extended range, where the linear magnetization law is no longer strictly valid. Moreover we compare for the first time results for mono- and polydisperse particles. For the latter, we observe an enhanced storage modulus in the linear regime of the magnetization.

The costs of schizophrenia in Spain.

This study estimated the economic impact of schizophrenia-related direct costs (medical and nonmedical costs) in Spain. Direct medical costs (hospitalizations, outpatient consultations, drug costs) and direct nonmedical costs (costs of informal care) were estimated based on prevalence costs for 2002. The total costs of schizophrenia were estimated at euro 1,970.8 million; direct medical costs accounted for 53% and informal care costs 47%. Despite having implemented a conservative approach, the health care costs associated with schizophrenia account for 2.7% of total public health care expenditure in Spain. The sum of medical and nonmedical costs give us a better definition of the magnitude of the problem in Spain as well as contributing to helping make the debate on this issue more transparent.