Entangled states are a key resource in fundamental quantum physics, quantum cryptography and quantum computation. Introduction of controlled unitary processes--quantum gates--to a quantum system has ...so far been the most widely used method to create entanglement deterministically. These processes require high-fidelity state preparation and minimization of the decoherence that inevitably arises from coupling between the system and the environment, and imperfect control of the system parameters. Here we combine unitary processes with engineered dissipation to deterministically produce and stabilize an approximate Bell state of two trapped-ion quantum bits (qubits), independent of their initial states. Compared with previous studies that involved dissipative entanglement of atomic ensembles or the application of sequences of multiple time-dependent gates to trapped ions, we implement our combined process using trapped-ion qubits in a continuous time-independent fashion (analogous to optical pumping of atomic states). By continuously driving the system towards the steady state, entanglement is stabilized even in the presence of experimental noise and decoherence. Our demonstration of an entangled steady state of two qubits represents a step towards dissipative state engineering, dissipative quantum computation and dissipative phase transitions. Following this approach, engineered coupling to the environment may be applied to a broad range of experimental systems to achieve desired quantum dynamics or steady states. Indeed, concurrently with this work, an entangled steady state of two superconducting qubits was demonstrated using dissipation.
Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron ...inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABAA receptors. We also observe that GABA neurons increase their firing in response to a footshock and provide evidence that driving GABA neurons with optogenetic effectors is sufficient to affect behavior. Taken together, our data demonstrate that synaptic inhibition of DA neurons drives place aversion.
► In the VTA, optogenetic activation of GABA neurons in vivo inhibits DA neurons ► A footshock excites GABA neurons and inhibits of a large majority of DA neurons ► The inhibition of DA neurons by a footshock is GABAA receptor dependent ► Activation of GABA neurons is sufficient to elicit conditioned place aversion
Tan et al. show that footshock induces GABA neuron excitation, leading to GABAA receptor-mediated inhibition of DA neurons. Optogenetic manipulation shows that VTA GABA neurons activation or direct inhibition of DA neurons is sufficient to drive behavioral aversion.
We report the fast growth of high-quality millimeter-size monolayer MoSe2 crystals on molten glass using an ambient pressure CVD system. We found that the isotropic surface of molten glass suppresses ...nucleation events and greatly improves the growth of large crystalline domains. Triangular monolayer MoSe2 crystals with sizes reaching ∼2.5 mm, and with a room-temperature carrier mobility up to ∼95 cm2/(V·s), can be synthesized in 5 min. The method can also be used to synthesize millimeter-size monolayer MoS2 crystals. Our results demonstrate that “liquid-state” glass is a highly promising substrate for the low-cost growth of high-quality large-size 2D transition metal dichalcogenides (TMDs).
Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds—urging the quest for predictive biomarkers. We hypothesize ...that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response.
In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients.
The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P<0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P=0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P<0.001), resulting in a 1-year survival difference of 24% (P=0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy.
These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.
Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, ...and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.
Purpose
Detection of peritoneal metastases (PM) is key in the staging and management of gastrointestinal and ovarian cancer patients. The purpose of this meta-analysis was to determine the diagnostic ...performance of CT, PET(CT), and (DW)MRI in detecting PM.
Methods
A literature search in Pubmed, Embase (Ovid), and Scopus was performed (January 1997–May 2018) to identify studies reporting on the accuracy of imaging PM in the diagnostic workup of gastrointestinal or ovarian cancers. Inclusion criteria were region-based or patient-based studies comprising > 15 patients, surgery/histology/radiological follow-up as a reference standard, and sufficient data to construct a 2 × 2 contingency table. Two observers performed data extraction. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model and hierarchical summary operating curves (HSROC) were generated.
Results
Of 3457 citations retrieved, twenty-four articles met all inclusion criteria. Thirty-seven datasets could be extracted for analysis including 20 for CT, 10 for PET(CT), and 7 for (DW)MRI. The pooled sensitivity, specificity, and DOR for the detection of PM for region-based studies for CT were 68% (CI, 46–84%), 88%(CI, 81–93%), and 15.9 (CI, 4.4–58.0) respectively; 80% (CI, 57–92%), 90% (CI, 80–96%), and 36.5 (CI, 6.7–199.5) for PET(CT), respectively; 92% (CI, 84–96%), 85% (CI, 78–91%), 63.3 (CI, 31.5–127.3) for (DW)MRI. In the patient-based group, not enough studies were included to make a pooled analysis for (DW)MRI and PET(CT).
Conclusion
(DW)MRI and PET(CT) showed comparable diagnostic performance for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients. Since MRI is more widely available than PET(CT) in clinical practice, this potentially is the imaging method of choice in most centers in the future.
Key Points
• Detection of peritoneal metastases plays an important role in the accurate staging of cancer patients, however, there is no accepted reference standard for the imaging of peritoneal metastases
• This meta-analysis shows that (DW)MRI provided the highest sensitivity for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients
• Although (DW)MRI and PET(CT) show a comparable overall diagnostic performance, (DW)MRI seems to be the imaging method of choice since it is more available in daily practice than PET(CT).
Background
Patients with limited peritoneal metastases from colorectal cancer may be candidates for an aggressive surgical approach including cytoreductive surgery and hyperthermic intraperitoneal ...chemotherapy (CRS–HIPEC). Selection is based on surgical inspection during laparoscopy or laparotomy. The aim of this study was to investigate whether diffusion‐weighted MRI (DW‐MRI) can be used to select patients for CRS–HIPEC.
Methods
This was a prospective study at a tertiary referral centre. Patients with confirmed or suspected colorectal peritoneal metastases scheduled for exploratory laparotomy or laparoscopy were eligible. Two radiologists assessed the peritoneal cancer index (PCI) on CT (CT‐PCI) and DW‐MRI (MRI‐PCI). The reference standard was PCI at surgery. Radiologists were blinded to the surgical PCI and to each other's findings. The main outcome was the accuracy of DW‐MRI in predicting whether patients had resectable disease (PCI less than 21) or not.
Results
Fifty‐six patients were included in the study, of whom 49 could be evaluated. The mean(s.d.) PCI at surgery was 11·27(7·53). The mean MRI‐PCI was 10·18(7·07) for reader 1 and 8·59(7·08) for reader 2. Readers 1 and 2 correctly staged 47 of 49 and 44 of 49 patients respectively (accuracy 96 and 90 per cent). Both readers detected all patients with resectable disease with a PCI below 21 at surgery (sensitivity 100 per cent). No patient was overstaged. The intraclass correlation (ICC) between readers was excellent (ICC 0·91, 95 per cent c.i. 0·77 to 0·96). MRI‐PCI had a stronger correlation with surgical PCI (ICC 0·83–0·88) than did CT‐PCI (ICC 0·39–0·44).
Conclusion
DW‐MRI is a promising non‐invasive tool to guide treatment selection in patients with peritoneal metastases from colorectal cancer.
Promising staging tool
Abstract
Background
Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was ...to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS).
Methods
Patients with cT1–2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value.
Results
Of 7382 registered patients with cT1–2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1–2 N1 respectively.
Conclusion
This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1–2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.
Graphical Abstract
This population-based study determined the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography. The results showed that preoperative MRI led to substantial overstaging in patients who underwent local excision or total mesorectal incision surgery for cT1–2 rectal cancer, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.
Graphical Abstract
Imaging weakness
Objective
Contrast-enhanced spectral mammography (CESM) examination results in a low-energy (LE) and contrast-enhanced image. The LE appears similar to a full-field digital mammogram (FFDM). Our aim ...was to evaluate LE CESM image quality by comparing it to FFDM using criteria defined by the European Reference Organization for Quality Assured Breast Screening and Diagnostic Services (EUREF).
Methods
A total of 147 cases with both FFDM and LE images were independently scored by two experienced radiologists using these (20) EUREF criteria. Contrast detail measurements were performed using a dedicated phantom. Differences in image quality scores, average glandular dose, and contrast detail measurements between LE and FFDM were tested for statistical significance.
Results
No significant differences in image quality scores were observed between LE and FFDM images for 17 out of 20 criteria. LE scored significantly lower on one criterion regarding the sharpness of the pectoral muscle (
p
< 0.001), and significantly better on two criteria on the visualization of micro-calcifications (
p
= 0.02 and
p =
0.034). Dose and contrast detail measurements did not reveal any physical explanation for these observed differences.
Conclusions
Low-energy CESM images are non-inferior to FFDM images. From this perspective FFDM can be omitted in patients with an indication for CESM.
Key Points
•
Low-energy CESM images are non-inferior to FFDM images.
•
Micro-calcifications are significantly more visible on LE CESM than on FFDM.
•
There is no physical explanation for this improved visibility of micro-calcifications.
•
There is no need for an extra FFDM when CESM is indicated.
The catalytic and magnetic properties of molybdenum disulfide (MoS2) are significantly enhanced by the presence of edge sites. One way to obtain a high density of edge sites in a two-dimensional (2D) ...film is by introducing porosity. However, the large-scale bottom-up synthesis of a porous 2D MoS2 film remains challenging and the correlation of growth conditions to the atomic structures of the edges is not well understood. Here, using molecular beam epitaxy, we prepare wafer-scale nanoporous MoS2 films under conditions of high Mo flux and study their catalytic and magnetic properties. Atomic-resolution electron microscopy imaging of the pores reveals two new types of reconstructed Mo-terminated edges, namely, a distorted 1T (DT) edge and the Mo-Klein edge. Nanoporous MoS2 films are magnetic up to 400 K, which is attributed to the presence of Mo-terminated edges with unpaired electrons, as confirmed by density functional theory calculation. The small hydrogen adsorption free energy at these Mo-terminated edges leads to excellent activity for the hydrogen evolution reaction.
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