Split Time Series into Patches: Rethinking Long-term Series Forecasting with Dateformer

Time is one of the most significant characteristics of time-series, yet has received insufficient attention. Prior time-series forecasting research has mainly focused on mapping a past subseries (lookback window) to a future series (forecast window), and time of series often just play an auxiliary role even completely ignored in most cases. Due to the point-wise processing within these windows, extrapolating series to longer-term future is tough in the pattern. To overcome this barrier, we propose a brand-new time-series forecasting framework named Dateformer who turns attention to modeling time instead of following the above practice. Specifically, time-series are first split into patches by day to supervise the learning of dynamic date-representations with Date Encoder Representations from Transformers (DERT). These representations are then fed into a simple decoder to produce a coarser (or global) prediction, and used to help the model seek valuable information from the lookback window to learn a refined (or local) prediction. Dateformer obtains the final result by summing the above two parts. Our empirical studies on seven benchmarks show that the time-modeling method is more efficient for long-term series forecasting compared with sequence modeling methods. Dateformer yields state-of-the-art accuracy with a 40% remarkable relative improvement, and broadens the maximum credible forecasting range to a half-yearly level

Wafer-Size and Single-Crystal MoSe_2 Atomically Thin Films Grown on GaN Substrate for Light Emission and Harvesting

Two-dimensional (2D) atomic-layered semiconductors are important for next-generation electronics and optoelectronics. Here, we designed the growth of an MoSe_2 atomic layer on a lattice-matched GaN semiconductor substrate. The results demonstrated that the MoSe_2 films were less than three atomic layers thick and were single crystalline of MoSe_2 over the entire GaN substrate. The ultrathin MoSe_2/GaN heterojunction diode demonstrated ∼850 nm light emission and could also be used in photovoltaic applications

Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase

Mcm2-7 helicase is loaded onto double-stranded origin DNA as an inactive double hexamer (DH) in G1 phase. The mechanisms of Mcm2-7 remodeling that trigger helicase activation in S phase remain unknown. Here, we develop an approach to detect and purify the endogenous DHs directly. Through cellular fractionation, we provide in vivo evidence that DHs are assembled on chromatin in G1 phase and separated during S phase. Interestingly, Mcm10, a robust MCM interactor, co-purifies exclusively with the DHs in the context of chromatin. Deletion of the main interaction domain, Mcm10 C terminus, causes growth and S phase defects, which can be suppressed through Mcm10-MCM fusions. By monitoring the dynamics of MCM DHs, we show a significant delay in DH dissolution during S phase in the Mcm10-MCM interaction-deficient mutants. Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell-cycle-regulated supercomplex with DHs

Ultrastrong Terahertz Emission from InN Nanopyramids on Single Crystal ZnO Substrates

The creation of high efficiency and room temperature terahertz (THz) emitters has long been expected in both scientific and industrial communities. Despite the recent progress in THz source such as quantum cascade lasers, high efficiency THz emitters capable of operating at room temperature are still elusive. Indium nitride (InN), a narrow bandgap semiconductor, has emerged as a promising THz emitter due to its unique electronic properties. However, the efficiency of InN THz emitters reported up to now is still far from theoretically predicted because of inadequately engineered electrical conduction and radiative coupling. In this study, the authors report a novel, high performance THz emitting structure consisting of nanoengineered InN micro/nanopyramid arrays on a single crystal zinc oxide (ZnO) substrate. With improved electronic conduction from Zn diffusion induced doping and enhanced radiation coupling benefiting from uniquely structured geometry, the InN nanopyramids yielded THz emission intensity is close to an order of magnitude stronger than that of p-type indium arsenide (InAs). These findings prove that InN is a promising THz material and of wide importance in material science, optical engineering sectors, etc

A pilot study of the use of dynamic analysis of cell-free DNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas

The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as applying ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies. However, the genetic alterations detected in cerebrospinal fluid ctDNA only partially overlapped with those from simultaneously collected AH/VF samples, with much lower allele frequencies. Serial post-treatment AH or VF samples were available for five patients and their changes in ctDNA allele frequency displayed a similar trend as the changes in interleukin-10 levels; an indicator of response to treatment. A cohort of 23 patients with primary central nervous system lymphoma was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of primary central nervous system lymphoma than VRL patients. The objective response rate to ibrutinib treatment was much higher for patients with primary central nervous system lymphoma (64.7%, 11/17) than for those with VRL (14.3%, 1/7). In summary, we provide valuable clinical evidence that AH is a good source of tumor genomic information and can substitute VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring

Synthetic lethality between TP53 and ENDOD1

The atypical nuclease ENDOD1 functions with cGAS-STING in innate immunity. Here we identify a previously uncharacterized ENDOD1 function in DNA repair. ENDOD1 is enriched in the nucleus following H2O2 treatment and ENDOD1−/− cells show increased PARP chromatin-association. Loss of ENDOD1 function is synthetic lethal with homologous recombination defects, with affected cells accumulating DNA double strand breaks. Remarkably, we also uncover an additional synthetic lethality between ENDOD1 and p53. ENDOD1 depletion in TP53 mutated tumour cells, or p53 depletion in ENDOD1−/− cells, results in rapid single stranded DNA accumulation and cell death. Because TP53 is mutated in ~50% of tumours, ENDOD1 has potential as a wide-spectrum target for synthetic lethal treatments. To support this we demonstrate that systemic knockdown of mouse EndoD1 is well tolerated and whole-animal siRNA against human ENDOD1 restrains TP53 mutated tumour progression in xenograft models. These data identify ENDOD1 as a potential cancer-specific target for SL drug discovery

Primary gastric non-Hodgkin's lymphoma in Chinese patients: clinical characteristics and prognostic factors

<p>Abstract</p> <p>Background</p> <p>Optimal management and outcome of primary gastric lymphoma (PGL) have not been well defined in the rituximab era. This study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in Chinese patients with PGL.</p> <p>Methods</p> <p>The clinicopathological features of 83 Chinese patients with PGL were retrospectively reviewed. Staging was performed according to the Lugano staging system for gastrointestinal non-Hodgkin's lymphoma.</p> <p>Results</p> <p>The predominant pathologic subtype among Chinese patients with PGL in our study was diffuse large B cell lymphoma (DLBCL), followed by mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 57 patients with gastric DLBCL, 20 patients (35.1%) were classified as the germinal center B cell-like (GCB) subtype and 37 patients (64.9%) as the non-GCB subtype. The 83 patients had a five-year overall survival (OS) and event-free survival (EFS) of 52% and 59%, respectively. Cox regression analysis showed that stage-modified international prognostic index (IPI) and performance status (PS) were independent predictors of survival. In the 67 B-cell lymphoma patients who received chemotherapy, 36 patients treated with rituximab (at least 3 cycles) had a mean OS of 72 months (95% CI 62-81) versus 62 months (95% CI 47-76) for patients without rituximab treatment (P = 0.021).</p> <p>Conclusion</p> <p>The proportion of Chinese gastric DLBCL cases with non-GCB subtype was higher than the GCB subtype. Stage-modified IPI and PS were effective prognostic factors in Chinese patients with PGL. Our data suggested that primary gastric B-cell lymphoma might have an improved outcome with rituximab in addition to chemotherapy. More studies are necessary, preferentially large prospective randomized clinical trials to obtain more information on the impact of the rituximab in the primary gastric B-cell lymphoma.</p

Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells

Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily, although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged, and are associated with elevated transcription of HERVH, a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors, including LBP9, recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts, including pluripotency-modulating long non-coding RNAs. Disruption of LBP9, HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs, and establish novel primate-specific transcriptional circuitry regulating pluripotency