Signatures of a surface spin-orbital chiral metal.

The relation between crystal symmetries, electron correlations and electronic structure steers the formation of a large array of unconventional phases of matter, including magneto-electric loop currents and chiral magnetism1-6. The detection of such hidden orders is an important goal in condensed-matter physics. However, until now, non-standard forms of magnetism with chiral electronic ordering have been difficult to detect experimentally7. Here we develop a theory for symmetry-broken chiral ground states and propose a methodology based on circularly polarized, spin-selective, angular-resolved photoelectron spectroscopy to study them. We use the archetypal quantum material Sr2RuO4 and reveal spectroscopic signatures that, despite being subtle, can be reconciled with the formation of spin-orbital chiral currents at the surface of the material8-10. As we shed light on these chiral regimes, our findings pave the way for a deeper understanding of ordering phenomena and unconventional magnetism.

Predictive Maintenance of Pins in the ECD Equipment for Cu Deposition in the Semiconductor Industry.

Nowadays, Predictive Maintenance is a mandatory tool to reduce the cost of production in the semiconductor industry. This paper considers as a case study a critical part of the electrochemical deposition system, namely, the four Pins that hold a wafer inside a chamber. The aim of the study is to replace the schedule of replacement of Pins presently based on fixed timing (Preventive Maintenance) with a Hardware/Software system that monitors the conditions of the Pins and signals possible conditions of failure (Predictive Maintenance). The system is composed of optical sensors endowed with an image processing methodology. The prototype built for this study includes one optical camera that simultaneously takes images of the four Pins on a roughly daily basis. Image processing includes a pre-processing phase where images taken by the camera at different times are coregistered and equalized to reduce variations in time due to movements of the system and to different lighting conditions. Then, some indicators are introduced based on statistical arguments that detect outlier conditions of each Pin. Such indicators are pixel-wise to identify small artifacts. Finally, criteria are indicated to distinguish artifacts due to normal operations in the chamber from issues prone to a failure of the Pin. An application (PINapp) with a user friendly interface has been developed that guides industry experts in monitoring the system and alerting in case of potential issues. The system has been validated on a plant at STMicroelctronics in Catania (Italy). The study allowed for understanding the mechanism that gives rise to the rupture of the Pins and to increase the time of replacement of the Pins by a factor at least 2, thus reducing downtime.

Mechanical and Enzymatic Digestion of Autologous Fat Grafting (A-FG): Fat Volume Maintenance and AD-SVFs Amount in Comparison.

BACKGROUND: Currently, several techniques for autologous fat graft (A-FG) preparation aimed at obtaining purified tissue exist. Both mechanical digestions via centrifugation, filtration, and enzymatic digestion were considered the most effective with different impacts in terms of adult adipose-derived stromal vascular fraction cells (AD-SVFs) amount that volume maintenance. OBJECTIVES: This article aimed to report the in vivo and in vitro results, represented by fat volume maintenance and AD-SVFs amount, obtained by four different procedures of AD-SVFs isolation and A-FG purification based on centrifugation, filtration, centrifugation with filtration, and enzymatic digestion. METHODS: A prospective, case-control study was conducted. In total, 80 patients affected by face and breast soft tissue defects were treated with A-FG and divided into four groups: n=20 were treated with A-FG enhanced with AD-SVFs obtained by enzymatic digestion (study group 1 [SG-1]); n=20 were treated with A-FG enhanced with AD-SVFs obtained by centrifugation with filtration (SG-2); n=20 were treated with A-FG enhanced with AD-SVFs obtained by only filtration (SG-3); n=20 were treated with A-FG obtained by only centrifugation according to the Coleman technique (control group [CG]). Twelve months after the last A-FG session, the volume maintenance percentage was analyzed by magnetic resonance imaging (MRI). Isolated AD-SVF populations were counted using a hemocytometer, and cell yield was reported as cell number/mL of fat. RESULTS: Starting with the same amount of fat analyzed (20 mL), 50,000 ± 6956 AD-SVFs/mL were obtained in SG-1; 30,250 ± 5100 AD-SVFs/mL in SG-2; 33.333 ± 5650 AD-SVFs/mL in SG-3, while 500 AD-SVFs/mL were obtained in CG. In patients treated with A-FG enhanced with AD-SVFs obtained by automatic enzymatic digestion, a 63% ± 6.2% maintenance of fat volume restoring after 1 year was observed compared with 52% ± 4.6% using centrifugation with filtration, 39% ± 4.4% using only centrifugation (Coleman), and 60% ± 5.0% using only filtration. CONCLUSIONS: In vitro AD-SVFs cell analysis indicated that filtration was the most efficient system-between mechanical digestion procedures-thanks to the highest amount of cells obtained with fewer cell structure damage, producing in vivo, the most volume maintenance after 1 year. Enzymatic digestion produced the best number of AD-SVFs and the best fat volume maintenance. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Low-Loss Integrated Nanophotonic Circuits with Layered Semiconductor Materials.

Monolayer transition-metal dichalcogenides with direct bandgaps are emerging candidates for optoelectronic devices, such as photodetectors, light-emitting diodes, and electro-optic modulators. Here we report a low-loss integrated platform incorporating molybdenum ditelluride monolayers with silicon nitride photonic microresonators. We achieve microresonator quality factors >3 × 106 in the telecommunication O- to E-bands. This paves the way for low-loss, hybrid photonic integrated circuits with layered semiconductors, not requiring heterogeneous wafer bonding.

Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration.

Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects.

Impact of the Different Preparation Methods to Obtain Autologous Non-Activated Platelet-Rich Plasma (A-PRP) and Activated Platelet-Rich Plasma (AA-PRP) in Plastic Surgery: Wound Healing and Hair Regrowth Evaluation.

Autologous therapies using platelet-rich plasma (PRP) need meticulous preparation-currently, no standardised preparation technique exists. Processing Quantitative Standards (PQSs) define manufacturing quantitative variables (such as time, volume and pressure). Processing Qualitative Standards (PQLSs) define the quality of the materials and methods of manufacturing. The aim of this review is to use existing PQSs and PQLs to report the in vivo/in vitro results obtained by using different Kits, that utilise different procedures (classified as Closed-Technique and Opened-Technique) to isolate autologous human activated (AA-PRP) or non-activated PRP (A-PRP). PQSs included the volumes of blood collected as well as the reagents used, the time/gravity of centrifugation, and the duration, temperature and tilt level/speed of centrifugation. PQLSs included the use of Calcium Chloride CaCl2, Kit weight, transparency of Kit components, the maintenance of a closed sterile processing environment and the use of a small centrifuge. Eight CE marked devices for PRP extraction were evaluated: Angel®, Biomed®, Cascade® and Selphyl®, Mag-18®, i-Stem®, MyCells® and Regenlab®. Using a Kit with the PQSs and PQLSs described in this study enables the isolation of A-PRP, thereby meeting consensus quality criteria. As our understanding of Critical Quality Attributes (CQAs) of A-PRP continues to evolve, especially with respect to purity and potency, adjustments to these benchmark PQSs and PQLs will hopefully help isolate A-PRP of desired CQAs with greater reproducibility, quality, and safety. Confirmatory studies will no doubt need to be completed.

Multi-Valley Superconductivity in Ion-Gated MoS2 Layers.

Layers of transition metal dichalcogenides (TMDs) combine the enhanced effects of correlations associated with the two-dimensional limit with electrostatic control over their phase transitions by means of an electric field. Several semiconducting TMDs, such as MoS2, develop superconductivity (SC) at their surface when doped with an electrostatic field, but the mechanism is still debated. It is often assumed that Cooper pairs reside only in the two electron pockets at the K/K' points of the Brillouin Zone. However, experimental and theoretical results suggest that a multivalley Fermi surface (FS) is associated with the SC state, involving six electron pockets at Q/Q'. Here, we perform low-temperature transport measurements in ion-gated MoS2 flakes. We show that a fully multivalley FS is associated with the SC onset. The Q/Q' valleys fill for doping ≳ 2 × 1013 cm-2, and the SC transition does not appear until the Fermi level crosses both spin-orbit split sub-bands Q 1 and Q 2. The SC state is associated with the FS connectivity and promoted by a Lifshitz transition due to the simultaneous population of multiple electron pockets. This FS topology will serve as a guideline in the quest for new superconductors.

Intravalley Spin-Flip Relaxation Dynamics in Single-Layer WS2.

In monolayer (1L) transition metal dichalcogenides (TMDs) the valence and conduction bands are spin-split because of the strong spin-orbit interaction. In tungsten-based TMDs the spin-ordering of the conduction band is such that the so-called dark excitons, consisting of electrons and holes with opposite spin orientation, have lower energy than A excitons. The transition from bright to dark excitons involves the scattering of electrons from the upper to the lower conduction band at the K point of the Brillouin zone, with detrimental effects for the optoelectronic response of 1L-TMDs, since this reduces their light emission efficiency. Here, we exploit the valley selective optical selection rules and use two-color helicity-resolved pump-probe spectroscopy to directly measure the intravalley spin-flip relaxation dynamics in 1L-WS2. This occurs on a sub-ps time scale, and it is significantly dependent on temperature, indicative of phonon-assisted relaxation. Time-dependent ab initio calculations show that intravalley spin-flip scattering occurs on significantly longer time scales only at the K point, while the occupation of states away from the minimum of the conduction band significantly reduces the scattering time. Our results shed light on the scattering processes determining the light emission efficiency in optoelectronic and photonic devices based on 1L-TMDs.

Electrically Controlled Nano and Micro Actuation in Memristive Switching Devices with On-Chip Gas Encapsulation.

Nanoactuators are a key component for developing nanomachinery. Here, an electrically driven device yielding actuation stresses exceeding 1 MPa withintegrated optical readout is demonstrated. 10 nm thick Al2 O3 electrolyte films are sandwiched between graphene and Au electrodes. These allow reversible room-temperature solid-state redox reactions, producing Al metal and O2 gas in a memristive-type switching device. The resulting high-pressure oxygen micro-fuel reservoirs are encapsulated under the graphene, swelling to heights of up to 1 µm, which can be dynamically tracked by plasmonic rulers. Unlike standard memristors where the memristive redox reaction occurs in single or few conductive filaments, the mechanical deformation forces the creation of new filaments over the whole area of the inflated film. The resulting on-off resistance ratios reach 108 in some cycles. The synchronization of nanoactuation and memristive switching in these devices is compatible with large-scale fabrication and has potential for precise and electrically monitored actuation technology.

On-Chip Integrated, Silicon-Graphene Plasmonic Schottky Photodetector with High Responsivity and Avalanche Photogain.

We report an on-chip integrated metal graphene-silicon plasmonic Schottky photodetector with 85 mA/W responsivity at 1.55 µm and 7% internal quantum efficiency. This is one order of magnitude higher than metal-silicon Schottky photodetectors operated in the same conditions. At a reverse bias of 3 V, we achieve avalanche multiplication, with 0.37A/W responsivity and avalanche photogain ∼2. This paves the way to graphene integrated silicon photonics.

Type-2 cannabinoid receptors in neurodegeneration.

Based on its wide expression in immune cells, type-2 cannabinoid (CB2) receptors were traditionally thought to act as "peripheral receptors" with an almost exclusively immunomodulatory function. However, their recent identification in mammalian brain areas, as well as in distinct neuronal cells, has opened the way to a re-consideration of CB2 signaling in the context of brain pathophysiology, synaptic plasticity and neuroprotection. To date, accumulated evidence from several independent preclinical studies has offered new perspectives on the possible involvement of CB2 signaling in brain and spinal cord traumatic injury, as well as in the most relevant neurodegenerative disorders like Alzheimer's disease, Parkinson's disease and Huntington's chorea. Here, we will review available information on CB2 in these disease conditions, along with data that support also its therapeutic potential to treat them.

Eight-fold signal amplification of a superconducting nanowire single-photon detector using a multiple-avalanche architecture.

Superconducting nanowire avalanche single-photon detectors (SNAPs) with n parallel nanowires are advantageous over single-nanowire detectors because their output signal amplitude scales linearly with n. However, the SNAP architecture has not been viably demonstrated for n > 4. To increase n for larger signal amplification, we designed a multi-stage, successive-avalanche architecture which used nanowires, connected via choke inductors in a binary-tree layout. We demonstrated an avalanche detector with n = 8 parallel nanowires and achieved eight-fold signal amplification, with a timing jitter of 54 ps.

Frozen adipose-derived mesenchymal stem cells maintain high capability to grow and differentiate.

In recent years, there has been a shift toward tissue-engineering strategies using stem cells for plastic and reconstructive surgical procedures. Therefore, it is important to develop safe and reproducible protocols for the extraction of adipose-derived stromal cells (ASCs) to allow cells to be stored in liquid nitrogen for future needs. The aspirated liposuction obtained from healthy donors were immediately processed after the suction using a protocol developed in our laboratory. The resulting stromal vascular fraction (SVF) was then characterized by the presence of adipose-derived stromal cells, at later stage frozen in liquid nitrogen. After that, cells were thawed and again characterized by adipose-derived stromal cells, cellular survival, differentiation ability and Colony Forming Unit-Fibroblast like colonies (CFU-F). Extraction and freezing of cells contained in the stromal vascular fraction demonstrate that thawed cells maintain the full capability to grow and differentiate in culture. The advent of adipose-derived stromal cells use in tissue engineering will assume a wide role in esthetic restoration in plastic surgery. It is thus important to develop clinically translatable protocols for the preparation and storage of adipose-derived stromal cells. Our results show that adipose-derived stromal cells in serum free can easily be frozen and stored in liquid nitrogen with retention of 85% of cell viability and 180,890 cell/g yield plus normal proliferative capacity and differentiation potential compared with fresh controls. These observations set the basis for adipose-derived stromal cells banking.

Mapping nanoscale carrier confinement in polycrystalline graphene by terahertz spectroscopy.

Terahertz time-domain spectroscopy (THz-TDS) can be used to map spatial variations in electrical properties such as sheet conductivity, carrier density, and carrier mobility in graphene. Here, we consider wafer-scale graphene grown on germanium by chemical vapor deposition with non-uniformities and small domains due to reconstructions of the substrate during growth. The THz conductivity spectrum matches the predictions of the phenomenological Drude-Smith model for conductors with non-isotropic scattering caused by backscattering from boundaries and line defects. We compare the charge carrier mean free path determined by THz-TDS with the average defect distance assessed by Raman spectroscopy, and the grain boundary dimensions as determined by transmission electron microscopy. The results indicate that even small angle orientation variations below 5° within graphene grains influence the scattering behavior, consistent with significant backscattering contributions from grain boundaries.

Radiometric Assay of ABHD2 Activity.

The α,ß-hydrolase fold-containing protein 2 (ABHD2) is a serine hydrolase, responsible for the cleavage of endogenous 2-arachidonoylglycerol (2-AG). ABHD2 is activated by progesterone, thus, it is considered a nonnuclear receptor of this steroid hormone that terminates its biological effects. The products of ABHD2-catalyzed cleavage by the natural substrate 2-AG are glycerol and arachidonic acid; here, instead of 2-AG, the radioactive substrate 2-oleoyl-[3H]glycerol has been used as already done in various acylglycerol lipase activity assays. The amount of [3H]glycerol released allows to measure ABHD2 enzymatic activity.

Chemical Proteomics Reveals Off-Targets of the Anandamide Reuptake Inhibitor WOBE437.

Anandamide or N-arachidonoylethanolamine (AEA) is a signaling lipid that modulates neurotransmitter release via activation of the type 1 cannabinoid receptor (CB1R) in the brain. Termination of anandamide signaling is thought to be mediated via a facilitated cellular reuptake process that utilizes a purported transporter protein. Recently, WOBE437 has been reported as a novel, natural product-based inhibitor of AEA reuptake that is active in cellular and in vivo models. To profile its target interaction landscape, we synthesized pac-WOBE, a photoactivatable probe derivative of WOBE437, and performed chemical proteomics in mouse neuroblastoma Neuro-2a cells. Surprisingly WOBE437, unlike the widely used selective inhibitor of AEA uptake OMDM-1, was found to increase AEA uptake in Neuro-2a cells. In line with this, WOBE437 reduced the cellular levels of AEA and related N-acylethanolamines (NAEs). Using pac-WOBE, we identified saccharopine dehydrogenase-like oxidoreductase (SCCPDH), vesicle amine transport 1 (VAT1), and ferrochelatase (FECH) as WOBE437-interacting proteins in Neuro-2a cells. Further genetic studies indicated that SCCPDH and VAT1 were not responsible for the WOBE437-induced reduction in NAE levels. Regardless of the precise mechanism of action of WOB437 in AEA transport, we have identified SSCPHD, VAT1, and FECH as unprecedented off-targets of this molecule which should be taken into account when interpreting its cellular and in vivo effects.

Chip-Scalable, Room-Temperature, Zero-Bias, Graphene-Based Terahertz Detectors with Nanosecond Response Time.

The scalable synthesis and transfer of large-area graphene underpins the development of nanoscale photonic devices ideal for new applications in a variety of fields, ranging from biotechnology, to wearable sensors for healthcare and motion detection, to quantum transport, communications, and metrology. We report room-temperature zero-bias thermoelectric photodetectors, based on single- and polycrystal graphene grown by chemical vapor deposition (CVD), tunable over the whole terahertz range (0.1-10 THz) by selecting the resonance of an on-chip patterned nanoantenna. Efficient light detection with noise equivalent powers <1 nWHz-1/2 and response time ∼5 ns at room temperature are demonstrated. This combination of specifications is orders of magnitude better than any previous CVD graphene photoreceiver operating in the sub-THz and THz range. These state-of-the-art performances and the possibility of upscaling to multipixel architectures on complementary metal-oxide-semiconductor platforms are the starting points for the realization of cost-effective THz cameras in a frequency range still not covered by commercially available microbolometer arrays.

High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene.

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from < 800 nm2 to 16 µm2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators.

Selective Fatty Acid Amide Hydrolase Inhibitors as Potential Novel Antiepileptic Agents.

Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a-m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a.

Combined Mastopexy and Augmentation with Autologous Fat Grafting: First Results with Lipopexy.

BACKGROUND: The treatment of breast ptosis and gland hypoplasia in a single surgery is a challenging procedure and the result is less predictable. In this surgery, the complications mainly concern the prosthesis, such as implant deflation, capsular contracture, palpability, or malposition. We, therefore, propose a different and new technique that avoids breast prosthesis, combining mastopexy and autologous augmentation with fat grafts. METHODS: Combined mastopexy and autologous fat graft augmentation (lipopexy) was performed in women affected by breast ptosis and asymmetric breast or hypomastia. The breast lift technique was determined due to the ptosis level. The process of fat grafting was executed according to the PureGraft and, in some cases, to GID System, to Celution System or Carraway's techniques. RESULTS: Thirty-four patients affected by breast ptosis and hypomastia underwent lipopexy from January 2010 to May 2017. The mean volume of adipose tissue injected for each breast was 225.98 ml. After surgery, the patients were followed for an average of 22.8 months. A mild ptosis relapse with partial fat absorption was observed in 4 cases (11.76%) and the presence of oily cysts was diagnosed in 2 patients (5.88%). One severe complication was recorded (hematoma drainage). All the patients healed uneventfully in 2 weeks. CONCLUSIONS: This technique allows the surgeon to distribute the desired fat volume along the breasts, avoids implants, and displayed stable results. This treatment has been demonstrated not to interfere with follow-up breast imaging. We, therefore, consider lipopexy a valuable and safe alternative to mastopexy and mild to moderate breast volume augmentation.