An outstanding goal in quantum optics and scalable photonic quantum technology is to develop a source that each time emits one and only one entangled photon pair with simultaneously high entanglement ...fidelity, extraction efficiency, and photon indistinguishability. By coherent two-photon excitation of a single InGaAs quantum dot coupled to a circular Bragg grating bull's-eye cavity with a broadband high Purcell factor of up to 11.3, we generate entangled photon pairs with a state fidelity of 0.90(1), pair generation rate of 0.59(1), pair extraction efficiency of 0.62(6), and photon indistinguishability of 0.90(1) simultaneously. Our work will open up many applications in high-efficiency multiphoton experiments and solid-state quantum repeaters.
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Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 ...promises to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its 'undruggable' nature and potentially limited selectivity. In a previous study, we reported an improved in silico approach targeting the DBD of STAT3 that resulted in a small-molecule STAT3 inhibitor (inS3-54). Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1. In this study, we describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound (inS3-54A18) with increased specificity and pharmacological properties. InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Thus inS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics targeting the DBD of human STAT3 and DBD of transcription factors may not be 'undruggable' as previously thought.
Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for ...quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS
2
with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS
2
as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.
The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
Drylands are home to more than 38% of the world's population and are one of the most sensitive areas to climate change and human activities. This review describes recent progress in dryland climate ...change research. Recent findings indicate that the long‐term trend of the aridity index (AI) is mainly attributable to increased greenhouse gas emissions, while anthropogenic aerosols exert small effects but alter its attributions. Atmosphere‐land interactions determine the intensity of regional response. The largest warming during the last 100 years was observed over drylands and accounted for more than half of the continental warming. The global pattern and interdecadal variability of aridity changes are modulated by oceanic oscillations. The different phases of those oceanic oscillations induce significant changes in land‐sea and north‐south thermal contrasts, which affect the intensity of the westerlies and planetary waves and the blocking frequency, thereby altering global changes in temperature and precipitation. During 1948–2008, the drylands in the Americas became wetter due to enhanced westerlies, whereas the drylands in the Eastern Hemisphere became drier because of the weakened East Asian summer monsoon. Drylands as defined by the AI have expanded over the last 60 years and are projected to expand in the 21st century. The largest expansion of drylands has occurred in semiarid regions since the early 1960s. Dryland expansion will lead to reduced carbon sequestration and enhanced regional warming. The increasing aridity, enhanced warming, and rapidly growing population will exacerbate the risk of land degradation and desertification in the near future in developing countries.
Key Points
Drylands are one of the most sensitive areas to climate change and human activities
Attribution of major drivers and processes to dryland climate change has been summarized
Enhanced warming, increasing aridity, and expanding drylands pose a threat to developing countries
Suppose that
(
X
,
d
,
μ
)
is a metric measure space of homogeneous type and
L
is a one-to-one operator of type
ω
on
L
2
(
X
)
, with
ω
∈
0
,
π
/
2
)
, which has a bounded holomorphic functional ...calculus, and whose heat kernel satisfies the Davies–Gaffney estimates. Suppose that
p
(
·
)
:
X
→
(
0
,
1
is a variable exponent function with the globally log-Hölder continuous condition. In this paper, we introduce the variable Hardy–Lorentz space
H
L
p
(
·
)
,
q
(
X
)
associated with
L
with
0
<
p
-
≤
p
+
≤
1
and
0
<
q
<
∞
, and establish its molecular characterization. Moreover, we study the dual spaces of
H
L
p
(
·
)
,
q
(
X
)
with
0
<
p
-
≤
p
+
≤
1
and
0
<
q
<
∞
.
Energy consumption in machining contributes a significant part of manufacturing cost and produces a great environmental impact. This paper provides a critical assessment on energy consumption in a ...machining system. Energy consumption is classified at the process, machine, and system levels. Machine tool power demand at different machine states by different components is also discussed. Then predictive methods of energy consumption at different levels are summarized. Finally, energy consumption reduction strategies are discussed to achieve sustainable manufacturing.
•Energy consumption is classified at the process, machine, and system levels.•The concept of net cutting energy is established.•Empirical and analytical models of energy consumption are critically analyzed.•The strategies for reducing energy consumption are recommended.
MicroRNAs are a class of small non-coding RNAs that have been implicated to mediate gene regulation in virtually all important biological processes. Recently there is accumulating evidence showing ...that miR-150 has essential regulatory roles in both normal and malignant hematopoiesis and holds great potential as a therapeutic target in treating various types of hematopoietic malignancies. The purpose of this review is to summarize our current knowledge about the expression patterns, biological functions and regulatory mechanisms of miR-150 in normal and malignant hematopoiesis, and to highlight the important questions to be answered in this burgeoning field.
Boson sampling is a well-defined task that is strongly believed to be intractable for classical computers, but can be efficiently solved by a specific quantum simulator. However, an outstanding ...problem for large-scale experimental boson sampling is the scalability. Here we report an experiment on boson sampling with photon loss, and demonstrate that boson sampling with a few photons lost can increase the sampling rate. Our experiment uses a quantum-dot-micropillar single-photon source demultiplexed into up to seven input ports of a 16×16 mode ultralow-loss photonic circuit, and we detect three-, four- and fivefold coincidence counts. We implement and validate lossy boson sampling with one and two photons lost, and obtain sampling rates of 187, 13.6, and 0.78 kHz for five-, six-, and seven-photon boson sampling with two photons lost, which is 9.4, 13.9, and 18.0 times faster than the standard boson sampling, respectively. Our experiment shows an approach to significantly enhance the sampling rate of multiphoton boson sampling.
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