Display omitted
•A deep transfer learning methodology based on Bi-LSTM is proposed for the first time to address the NIR model transfer issue for samples produced in different conditions.•Bi-LSTM ...modeling outperformed1D-CNN, PLS and ELM for source manure and γ-PGA cases.•Transfer learning by fine-tuning Bi-LSTM layers and re-training FC layers performed even better than by fixing Bi-LSTM layers and only re-training FC layers.•A Bi-LSTM-fine-tuning enabled NIRS technology is beneficial to improve the adaptability of NIR spectroscopy in various new application scenarios.
This study proposed a deep transfer learning methodology based on an improved Bi-directional Long Short-Term Memory (Bi-LSTM) network for the first time to address the near infrared spectroscopy (NIR) model transfer issue between samples. We tested its effectiveness on two datasets of manure and polyglutamic acid (γ-PGA) solution, respectively. First, the optimal primary Bi-LSTM networks for cattle manure and the first batch of γ-PGA were developed by ablation experiments and both proved to outperform one-dimensional convolutional neural network (1D-CNN), Partial Least Square (PLS) and Extreme Learning Machine (ELM) models. Then, two types of transfer learning approaches were carried out to determine model transferability to non-homologous samples. For poultry manure and the second batch of γ-PGA, the obtained predicting results verified that the second approach of fine-tuning Bi-LSTM layers and re-training FC layers transcended the first approach of fixing Bi-LSTM layers and only re-training FC layers by reducing the RMSEPtarget of 23.4275% and 50.7343%, respectively. Finally, comparisons with fine-tuning 1D-CNN and other traditional model transfer methods further identified the superiority of the proposed methodology with exceeding accuracy and smaller variation, which decreased RMSEPtarget of poultry manure and the second batch of γ-PGA of 7.2832% and 48.1256%, 67.1117% and 80.6924% when compared to that acquired by fine-tuning 1D-CNN, Tradaboost-ELM and CCA-PLS which were the best of five traditional methods, respectively. The study demonstrates the potential of the Fine-tuning-Bi-LSTM enabled NIR technology to be used as a simple, cost effective and reliable detection tool for a wide range of applications under various new scenarios.
ARID1A is a core DNA-binding subunit of the BAF chromatin remodeling complex, and is lost in up to 7% of all cancers. The frequency of ARID1A loss increases in certain cancer types, such as clear ...cell ovarian carcinoma where ARID1A protein is lost in about 50% of cases. While the impact of ARID1A loss on the function of the BAF chromatin remodeling complexes is likely to drive oncogenic gene expression programs in specific contexts, ARID1A also binds genome stability regulators such as ATR and TOP2. Here we show that ARID1A loss leads to DNA replication stress associated with R-loops and transcription-replication conflicts in human cells. These effects correlate with altered transcription and replication dynamics in ARID1A knockout cells and to reduced TOP2A binding at R-loop sites. Together this work extends mechanisms of replication stress in ARID1A deficient cells with implications for targeting ARID1A deficient cancers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo ...glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.
Display omitted
•Comparisons of NSCs and derivative GSCs reveal elevated WNT5A and EC signature•PAX6/DLX5 bidirectionally regulates WNT5A during differentiation of GSCs into GdECs•WNT5A-mediated GdEC differentiation and EC recruitment support GSC invasive growth•Clinical studies of peritumoral/recurrent GBM reveal increased WNT5A/GdEC expression
Epigenetic activation of WNT5A expression contributes to glioblastoma tumor recurrence by promoting differentiation of glioma-derived stem cells into endothelial cells.
Transparent conductive oxides (TCOs) such as indium-tin oxide (ITO) have attracted increasing interests in integrated photonics and silicon photonics, owing to their large plasma dispersion and ...epsilon-near-zero (ENZ) effect. The nonlinear change of refractive index induced by free carrier modulation leads to a large electro-optic modulation with ultra-compact device footprint and unprecedented energy efficiency. However, high-speed modulation result is rare, mainly due to the lack of high-speed device design and fabrication quality. In this article, we characterize the fundamental electro-optic modulation structure consisting of Au/ITO/oxide/p-Si capacitor, showing that the property of ITO is greatly affected by the process condition. We also report an 8-μm-long hybrid plasmonic-silicon modulator driven by an ENZ ITO capacitor, achieving 100fJ/bit energy efficiency, 3.5 GHz modulation bandwidth, and 4.5 Gb/s data rate. The electro-absorption modulator covers a broad optical bandwidth from 1515 to 1580 nm wavelength. For future development of such modulators, we point out that by replacing ITO with higher mobility TCO materials, we can achieve 40 GHz modulation bandwidth and 0.4 fJ/bit energy efficiency using a 3-μm-long device.
Silicon photonic modulators rely on the plasma dispersion effect by free-carrier injection or depletion, which can only induce moderate refractive index perturbation. Therefore, the size and energy ...efficiency of silicon photonic modulators are ultimately limited as they are also subject to the diffraction limit. Here we report an ultracompact electro-optic modulator with total device footprint of 0.6 × 8 μm2 by integrating voltage-switched transparent conductive oxide with one-dimensional silicon photonic crystal nanocavity. The active modulation volume is only 0.06 um3, which is less than 2% of the lambda-cubic volume. The device operates in the dual mode of cavity resonance and optical absorption by exploiting the refractive index modulation from both the conductive oxide and the silicon waveguide induced by the applied gate voltage. Such a metal-free, hybrid silicon-conductive oxide nanocavity modulator also demonstrates only 0.5 dB extra optical loss, moderate Q-factor above 1000, and high energy efficiency of 46 fJ/bit. The combined results achieved through the holistic design opened a new route for the development of next generation electro-optic modulators that can be used for future on-chip optical interconnects.
Abstract
Indoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly ...because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC). Overexpression of USP14 promotes tryptophan metabolism and T-cell dysfunction by stabilizing the IDO1 protein. Knockdown of USP14 or pharmacological targeting of USP14 decreases IDO1 expression, reverses suppression of cytotoxic T cells, and increases responsiveness to anti-PD-1 in a MC38 syngeneic mouse model. Importantly, suppression of USP14 has no effects on AhR activation induced by the IDO1 inhibitor. These findings highlight a relevant role of USP14 in post-translational regulation of IDO1 and in the suppression of antitumor immunity, suggesting that inhibition of USP14 may represent a promising strategy for CRC immunotherapy.
We present an indoor free-space optical communication system to augment traditional short-range radio frequency wireless links. In this system, we integrated a high-frequency, high-current laser ...driver with an 850 nm wavelength, 500 mW vertical cavity surface emitting laser (VCSEL) array to transmit high speed optical signals with a large spatial coverage. The large current-bandwidth capability of the laser driver is enabled by a distributed current driver design utilizing three enhanced-mode pseudomorphic high electron mobility transistors. At the optical receiver end, a high-sensitivity avalanche photodiode is used to achieve high speed optical signal detection without any light concentrating optical device and is tolerant to angular deviation up to 27°. The communication link described in this article forms an optical femtocell with an area of 100 cm 2 at a distance of three meters from the transmitter. A bit error rate of less than 10 −4 is achieved throughout the optical femtocell in a normal in-door environment. On-off-keying and four-level pulse amplitude modulation schemes are both implemented with 1.25 Gb/s and 2 Gb/s data rate respectively, using the hardware described in this article. Additionally, the overall performance of this free-space optical link is evaluated in terms of viewing angle, distance range, and bit error rate.
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As ...loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.
To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients.
The institutional cardiopulmonary ...exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA.
A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI.
In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.
We present a dual-mode readout sensing mechanism that can effectively distinguish true and false-positive signals of melamine in milk by combining colorimetric analysis and surface-enhanced Raman ...scattering (SERS) spectroscopy. The colorimetry analysis takes advantage of color change of plasmonic nanoparticles upon the presence of melamine. We discovered that Ag colloids with 20 nm diameter was suitable for both colorimetric and SERS methods. However, the colorimetric method may present false-positive signals with the presence of interfering compounds. SERS spectroscopy can overcome this limitation and directly obtain signature spectra from the same plasmonic NPs used for the colorimetric assay without any modification. Melamine/s-triazine can be reliably differentiated by probing the SERS spectra based on surface-selection rules. The limit of detection of sensing melamine from milk by this method could reached to 0.05 ppm. Therefore, the combination of colorimetric and SERS method not only allows for rapid preliminary screening of melamine by naked eyes, but also greatly reduces false-positive signals by surface selection rules in SERS.
Display omitted
•A colorimetric and SERS dual-readout biosensor base on plasmonic Ag NPs•Distinguishing true and false-positive results by surface selection rules in SERS•Successful application for monitoring melamine in milk
PDF
