Low-loss and broadband polarization-diversity edge coupler on a thin-film lithium niobate platform.

Fiber-to-chip coupling is an essential issue for taking high-performance integrated photonic devices into practical applications. On a thin-film lithium niobate platform, such a high-performance coupler featuring low loss, large bandwidth, and polarization independence is highly desired. However, the mode hybridization induced by the birefringence of lithium niobate seriously restricts a polarization-independent coupling. Here, we propose and experimentally demonstrate a high-performance and polarization-diversity cantilever edge coupler (EC) with the assistance of a two-stage polarization splitter and rotator (PSR). The fabricated cantilever EC shows a minimal coupling loss of 1.06 dB/facet, and the fully etched PSR structure shows a low insertion loss (IL) of -0.62 dB. The whole polarization-diversity cantilever EC exhibits a low IL of -2.17 dB and -1.68 dB for TE0 and TM0 mode, respectively, as well as a small cross talk of <-15 dB covering the wavelength band from 1.5 µm to 1.6 µm. A polarization-dependent loss <0.5 dB over the same wavelength band is also obtained. The proposed fiber-to-waveguide coupler, compatible with the fabrication process of popular thin-film lithium niobate photonic devices, can work as a coupling scheme for on-chip polarization-diversity applications.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Compact 100GBaud driverless thin-film lithium niobate modulator on a silicon substrate.

Electro-optic (EO) modulators with a high modulation bandwidth are indispensable parts of an optical interconnect system. A key requirement for an energy-efficient EO modulator is the low drive voltage, which can be provided using a standard complementary metal oxide semiconductor circuity without an amplifying driver. Thin-film lithium niobate has emerged as a new promising platform, and shown its capable of achieving driverless and high-speed EO modulators. In this paper, we report a compact high-performance modulator based on the thin-film lithium niobate platform on a silicon substrate. The periodic capacitively loaded travelling-wave electrode is employed to achieve a large modulation bandwidth and a low drive voltage, which can support a driverless single-lane 100Gbaud operation. The folded modulation section design also helps to reduce the device length by almost two thirds. The fabricated device represents a large EO bandwidth of 45GHz with a half-wave voltage of 0.7V. The driverless transmission of a 100Gbaud 4-level pulse amplitude modulation signal is demonstrated with a power consumption of 4.49fj/bit and a bit-error rate below the KP4 forward-error correction threshold of 2.4×10-4.

Another Record: Ocean Warming Continues through 2021 despite La Niña Conditions.

The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year's record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.

Propagation properties of autofocusing off-axis hollow vortex Gaussian beams in free space.

By solving the (2 + 1) dimensional Schrödinger equation in free space, we find that the autofocusing off-axis hollow vortex Gaussian beams (HVGBs) are analytically derived for the first time. The off-axis HVGBs can be adjusted by changing the off-axis coordinate (x0,y0) and topological charge n2. In particular, by increasing the off-axis coordinate (x0,y0), the self-focusing intensity can be increased. Besides, the self-focusing property can be more obvious. Furthermore, by increasing the hollow order n1, we can deepen the depth of focus, make the focus position further away, and increase the self-focusing intensity too. We also discuss other propagation properties that are used to enrich the autofocusing off-axis HVGBs, such as Poynting vector, angular momentum, gradient force, and maximum scattering force during propagation.

Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity.

Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using CRBN65 antibody and TaqMan quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and mRNA levels. Furthermore, lack of correlation between cereblon expression in MM cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity.

OBJECTIVE: To evaluate if berberine can act on vitamin D receptors (VDR) and thereby regulate the expression of tight junction proteins (TJPs) in irritable bowel syndrame-diarrhea-predominant (IBS-D) rats. METHODS: The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation. After modeling, the model was evaluated and rats were divided into the control group and berberine treatment groups (0.85, 1.7 and 3.4 mg/kg, once a day for 2 weeks). The distal colon was obtained and colonic epithelial cells (CECs) were isolated and cultured after IBS-D model evaluation. The vitamin D receptor response element (VDRE) reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter. VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair, and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs. RESULTS: The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner (P<0.05). The activity of VDRE promoter was also effectively promoted by berberine (P<0.05). Berberine increased the expression of TJPs in IBS-D CECs (P<0.05). VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups (all P<0.05). RT-qPCR and Western blot results showed that compared with the blank group, expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups (all P<0.05). Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1 (P<0.05). CONCLUSION: Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity, and the main site of action is the N-terminal region of VDR.

Anisotropy-free arrayed waveguide gratings on X-cut thin film lithium niobate platform of in-plane anisotropy.

Arrayed waveguide grating is a versatile and scalable integrated light dispersion device, which has been widely adopted in various applications, including, optical communications and optical sensing. Recently, thin-film lithium niobate emerges as a promising photonic integration platform, due to its ability of shrinking largely the size of typical lithium niobate based optical devices. This would also enable multifunctional photonic integrated chips on a single lithium niobate substrate. However, due to the intrinsic anisotropy of the material, to build an arrayed waveguide grating on X-cut thin-film lithium niobate has never been successful. Here, a universal strategy to design anisotropy-free dispersive components on a uniaxial in-plane anisotropic photonic integration platform is introduced for the first time. This leads to the first implementation of arrayed waveguide gratings on X-cut thin-film lithium niobate with various configurations and high-performances. The best insertion loss of 2.4 dB and crosstalk of -24.1 dB is obtained for the fabricated arrayed waveguide grating devices. Applications of such arrayed waveguide gratings as a wavelength router and in a wavelength-division multiplexed optical transmission system are also demonstrated.

Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China.

BACKGROUND: Schistosomiasis transmission is typically focal. Understanding spatial variations of Schistosoma infections and their associated factors is important to help to invent site-specific intervention strategies. METHODS: A five-year longitudinal study was carried out prospectively in 12 natural villages, Guichi district of Anhui province. A GIS-based spatial analysis was conducted to identify geographic distribution patterns of schistosomiasis infections at the household scale. RESULTS: The results of the spatial autocorrelation analysis for 2005 showed that there were significant spatial clusters of human infections at the household level, and these results were in agreement with that of the spatial scan statistic. As prevalence of infections in humans decreased over the course of control, the spatial distribution of these infections became less heterogeneous. CONCLUSIONS: The findings imply that it may be necessary to re-assess risk factors of S. japonicum transmission over the course of control and to adjust accordingly control measures in the communities.

[Evaluation on the effect of comprehensive control strategy of schistosomiasis with emphasis on infection source control in Anhui province].

OBJECTIVE: To evaluate the effect of comprehensive control strategy of schistosomiasis with emphasis on infection source control in Anhui province. METHODS: Forty endemic villages in Guichi district, Chizhou city, Anhui province were selected as national pilot villages in the years from 2006 to 2008, and another 10 provincial pilot villages were respectively selected from 10 highly endemic villages in 7 cities in 2007. The comprehensive infection source control measures, including "replace cattle with machines", "raise livestock in pens", "improve the sanitary toilets", "supply safe water " and so on were carried out among the above pilot villages. At the end of 2008, 13 national pilot villages and 6 provincial pilot villages were selected to investigate the popularity of schistosomiasis, and the effect of the comprehensive control strategy in those villages were compared. RESULTS: After implementing the comprehensive control strategy, the infectious rate of schistosomiasis in national pilot villages decreased from 4.57% (487/10 659) to 1.76% (147/8370), with the reduction rate at 61.49%, whose difference showed statistical significance (χ(2) = 115.16, P < 0.01); and the density of infected snails decreased from 0.0067/0.1 m(2) to 0.0008/0.1 m(2), the infectious rate of snails decreased from 0.28% to 0.04%, whose reduction rates were 88.06% and 85.71% respectively. While as to the provincial pilot villages, the infectious rate of schistosomiasis decreased from 1.27% (54/4254) to 0.21% (14/6592), with the reduction rate at 83.46%, whose difference showed statistical significance (χ(2) = 94.57, P < 0.01); and the density of infected snails decreased from 0.0025/0.1 m(2) to 0.0003/0.1 m(2), the infection rate of snails decreased from 0.13% to 0.05%, whose reduction rates were 88.00% and 61.54% respectively. CONCLUSION: The comprehensive control strategy with emphasis on infection source control implemented in marshland and lake regions can effectively control the transmission of schistosomiasis.

Stochastic Simulation of Typhoon in Northwest Pacific Basin Based on Machine Learning.

Typhoons have caused serious economic losses and casualties in coastal areas all over the world. The big size of the tropical cyclone sample by stochastic simulation can effectively evaluate the typhoon hazard risk, and the typhoon full-track model is the most popular model for typhoon stochastic simulation. Based on the advantages of machine learning in dealing with nonlinear problems, this study uses a backpropagation neural network (BPNN) to replace the regression model in the empirical track model, reestablishes the neural network model for track and intensity prediction in typhoon stochastic simulation, and constructs full-track typhoon events of 1000 years for Northwest Pacific basin. The validation results indicate that the BPNN can improve the accuracy of typhoon track and intensity prediction.

Crochet Hook Technique for Arthroscopic Anterior Talofibular Ligament Repair: Technique Note.

Ankle sprains can lead to chronic lateral ankle instability caused by an injured anterior talofibular ligament (ATFL), and surgery is often required when conservative treatments fail. BROSTROM surgery is considered the gold standard and has a definite curative effect. Advancements in arthroscopic surgery and improvements in implanted anchors have led to an increase in ATFL repairs using arthroscopic surgery. Arthroscopic AFTL repair is less invasive, and patients could experience faster recovery compared to open AFTL repair. To simplify the complicated suture-passing processes in arthroscopic AFTL repair, we developed a crochet hook and loop wire technique, which is described in this paper.

Surface warming-induced global acceleration of upper ocean currents.

How the ocean circulation changes in a warming climate is an important but poorly understood problem. Using a global ocean model, we decompose the problem into distinct responses to changes in sea surface temperature, salinity, and wind. Our results show that the surface warming effect, a robust feature of anthropogenic climate change, dominates and accelerates the upper ocean currents in 77% of the global ocean. Specifically, the increased vertical stratification intensifies the upper subtropical gyres and equatorial currents by shoaling these systems, while the differential warming between the Southern Ocean upwelling zone and the region to the north accelerates surface zonal currents in the Southern Ocean. In comparison, the wind stress and surface salinity changes affect regional current systems. Our study points a way forward for investigating ocean circulation change and evaluating the uncertainty.

Management of anticoagulants in delayed bleeding after endoscopic resection: A systematic review and meta-analysis.

Background and study aims Delayed bleeding and thrombotic events are uncontrolled adverse events that are hard to balance in patients receiving anticoagulants after endoscopic resection. The present study aims to assess the clinical effect of warfarin, when compared to direct oral anticoagulants (DOACs), in terms of delayed bleeding and thrombotic events. Methods A comprehensive electronic literature search was conducted for eligible literature. Pairwise meta-analyses were performed on outcomes of delayed bleeding and thrombotic events. Two networks within the Bayesian framework were established based on the management of anticoagulants and type of DOAC. Results Eight cohort studies with 2,046 patients were eligible for inclusion, including 1,176 patients treated with warfarin and 870 with DOACs. There was no significant difference between warfarin and DOACs, in terms of delayed bleeding (OR = 1.29, 95 % CI [0.99-1.69]) and thromboembolism (OR = 2.0, 95 % CI [0.32-12.39]). In the network meta-analyses for delayed bleeding, the rank probabilities revealed that the safest management was discontinuous warfarin without heparin bridge therapy (HBT). Rank probabilities for the types of DOACs demonstrated that the safest drug was dabigatran. Conclusions There was no significant difference in delayed bleeding and thromboembolism between warfarin and DOACs in patients receiving endoscopic treatment. In terms of delayed bleeding, discontinuous warfarin without HBT was suggested as the best management, and dabigatran was recommended as the best type of DOAC.

Robust-linear-model normalization to reduce technical variability in functional protein microarrays.

Protein microarrays are similar to DNA microarrays; both enabling the parallel interrogation of thousands of probes immobilized on a surface. Consequently, they have benefited from technologies previously developed for DNA microarrays. However, assumptions for the analysis of DNA microarrays do not always translate to protein arrays, especially in the case of normalization. Hence, we have developed an experimental and computational framework to assess normalization procedures for protein microarrays. Specifically, we profiled two sera with markedly different autoantibody compositions. To analyze intra- and interarray variability, we compared a set of control proteins across subarrays and the corresponding spots across multiple arrays, respectively. To estimate the degree to which the normalization could help reveal true biological separability, we tested the difference in the signal between the sera relative to the variability within replicates. Next, by mixing the sera in different proportions (titrations), we correlated the reactivity of proteins with serum concentration. Finally, we analyzed the effect of normalization procedures on the list of reactive proteins. We compared global and quantile normalization, techniques that have traditionally been employed for DNA microarrays, with a novel normalization approach based on a robust linear model (RLM) making explicit use of control proteins. We show that RLM normalization is able to reduce both intra- and interarray technical variability while maintaining biological differences. Moreover, in titration experiments, RLM normalization enhances the correlation of protein signals with serum concentration. Conversely, while quantile and global normalization can reduce interarray technical variability, neither is as effective as RLM normalization in maintaining biological differences. Most importantly, both introduce artifacts that distort the signals and affect the correct identification of reactive proteins, impairing their use for biomarker discovery. Hence, we show RLM normalization is better suited to protein arrays than approaches used for DNA microarrays.

Identification of synaptic targets of Drosophila pumilio.

Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3'UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3'UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage.

Elimination of Schistosoma japonicum Transmission in China: A Case of Schistosomiasis Control in the Severe Epidemic Area of Anhui Province.

Over the several decades, China has been incessantly optimizing control strategies in response to the varying epidemic situations of schistosomiasis. We evaluated continuously the changing prevalence under different control strategies of two villages, Sanlian and Guifan, in China through five phases lasting 37 years. We tested residents, calculated prevalence and discussed change causes. We found the prevalence in Sanlian did not differ significant from that of Guifan (p = 0.18) in 1981, but decreased to 2.66%, much lower than Guifan's 11.25%, in 1984 (p = 0). Besides, prevalence in Guifan increased to 21.25% in 1987, while in Sanlian it rose to 20.78% until 1989. Those data confirmed that praziquantel combined with snail control could better reduce the prevalence. From 1992 to 1994, the prevalence in the two villages displayed downtrends, which showed the World Bank Loan Project worked. From 1995 to 2004, repeated oscillations with no obvious change trend was seen. Since 2005, the prevalence in both villages has shown a significant downtrend (p < 0.05), which suggests the integrated strategy is effective. We considered the control strategies were implemented suitably in the study area under changing social circumstances. Adjusting the strategy in consideration of social transformations is necessary and vital. The experience may be useful for policy making of other epidemic areas with an analogous situation.

[Study on the quantified indices to describe the distributional status of diseases in the spatial point pattern analysis].

OBJECTIVE: To study the quantified indices for describing the distributional status of diseases in the spatial point pattern analysis, and provide the a statistic in disease prevention and control. METHODS: G function, F function, J function and K function were summarized based on the inter-case distances from the view of spatial point pattern analysis. Through the introduction of the basic principles, these were used to analyze the data of acute schistosomiasis in the Guichi District, Chizhou City, Anhui province, with the study distances being from 0 to 3000 meters with 50-meter intervals. The findings were also validated by means of spatial moving scan window performed in SaTScan software. RESULTS: A total of 83 cases of acute schistosomiasis identified in Guichi District, and the point map showed that these cases were mainly distributed around the Yangtze and Qiupu rivers. The computational methods and characteristics of the four quantified indices were obtained. These acute schistosomiasis cases were also explored by using these indices, and the results showed that C and K functions were above 95% confidence interval. While, F and J functions were below 95% confidence interval. Ml these four indices showed that spatial clustering existed in the acute cases, which was consistent with the results of spatial moving scan window method. The latter method also found a most likely cluster, the coordinate of the circle center is (30.65 N, 117.44 E), radius is 2.69 km, and relative risk is 12.78 (DIR = 32. 80, P = 0. 0001). CONCLUSION: The quantified indices to describe the distributional status of diseases have not only solved the obstacle that spatial point pattern map which could only be analyzed qualitatively, but also supplied a theoretical foundation to deepen spatial clustering analysis. OBJECTIVE: To study the quantified indices for describing the distributional status of

[Scan statistic method with moving window and its application in the temporal clustering detection of acute schistosomiasis].

Acute schistosomiasis cases from 2001 to 2006 in Guichi District, Chizhou City, Anhui Province, were collected and analyzed by scan statistic method with moving window, central degree approach and circular distribution method in order to detect the temporal clustering of schistosomiasis. The analyzed data provided by the method showed that the temporal clustering of acute schistosomiasis from 2001 to 2003 in Guichi District became more concentrative, and then disperse, resulting in a final disappearance of the clustering in 2006 (LLR = 4.14, P > 0.05). The temporal clustering for all cases in the six years detected by scan statistic method was between August to September in 2002 (LLR = 18.5, P < 0.01), which was consistent with the real condition. Whereas the results from the central degree and the circular distribution methods could only provide limited information and were biased in the analysis in 2002, indicating that the scan statistic method with moving window can provide ample information with more robust and credible results.