A systematic analysis of regression models for protein engineering.

To optimize proteins for particular traits holds great promise for industrial and pharmaceutical purposes. Machine Learning is increasingly applied in this field to predict properties of proteins, thereby guiding the experimental optimization process. A natural question is: How much progress are we making with such predictions, and how important is the choice of regressor and representation? In this paper, we demonstrate that different assessment criteria for regressor performance can lead to dramatically different conclusions, depending on the choice of metric, and how one defines generalization. We highlight the fundamental issues of sample bias in typical regression scenarios and how this can lead to misleading conclusions about regressor performance. Finally, we make the case for the importance of calibrated uncertainty in this domain.

Maskless photolithography based on ultraviolet micro-LEDs and direct writing method for improving pattern resolution.

Ultraviolet micro-LEDs show great potential as a light source for maskless photolithography. However, there are few reports on micro-LED based maskless photolithography systems, and the studies on the effects of system parameters on exposure patterns are still lacking. Hence, we developed a maskless photolithography system that employs micro-LEDs with peak wavelength 375 nm to produce micrometer-sized exposure patterns in photoresists. We also systematically explored the effects of exposure time and current density of micro-LED on static direct writing patterns, as well as the effects of stage velocity and current pulse width on dynamic direct writing patterns. Furthermore, reducing the size of micro-LED pixels enables obtaining high-resolution exposure patterns, but this approach will bring technical challenges and high costs. Therefore, this paper proposes an oblique direct writing method that, instead of reducing the micro-LED pixel size, improves the pattern resolution by changing the tilt angle of the sample. The experimental results show that the linewidths of the exposed lines decreased by 4.0% and 15.2%, respectively, as the sample tilt angle increased from 0° to 15° and 30°, which confirms the feasibility of the proposed method to improve the pattern resolution. This method is also expected to correct the exposure pattern error caused by optical distortion of the lens in the photolithography system. The system and method reported can be applied in various fields such as PCBs, photovoltaics, solar cells, and MEMS.

Temperature-dependent electroluminescence of red high-In-content MQWs of dual-wavelength micro-LED.

Temperature-dependent electroluminescence (TDEL) measurements have been employed to investigate the carrier transport and recombination processes of InGaN red micro-LED based on dual-wavelength InGaN/GaN MQWs structure. EL peak energy and carrier transport of the red micro-LED both show temperature dependence, due to temperature-induced changes in defect activation. In addition, the current density at which the blue peak of the low-In-content appears in the EL spectrum varies with temperature. As the temperature increases, the blue peak of the low In component tends to appear at higher current densities, which may be attributed to the increase in thermally activated defects hindering the injection of holes into the low-In-content MQWs further away from p-GaN. Furthermore, the IQEs of the high-In-content MQWs are estimated from the TDEL method and then reveal the temperature-dependent efficiency droop. The IQE decreases as temperature increases, particularly above 50 K, where it drops sharply due to temperature-dependent nonradiative recombination. And the two different variation trends in IQE of MQWs with high and low In content reveal a competitive mechanism in carrier distribution, implying that more escaping holes from high-In-content MQWs will further reduce red emission efficiency but enhance carrier injection and blue emission in low-In-content MQWs.

Improvements of the modulation bandwidth and data rate of green-emitting CsPbBr3 perovskite quantum dots for Gbps visible light communication.

CsPbBr3 perovskite quantum dots (PQDs) as promising color conversion materials have been widely used in display and visible light communication (VLC), but most CsPbBr3 PQDs for VLC are randomly selected without optimization. Thereby the exploration of fundamental experimental parameters of QDs is essential to better employ their performance advantages. Herein, we investigated the concentration and solvent effects on photoluminescence (PL) properties and communication performance of CsPbBr3 PQDs. The PL, time-resolved PL characterization and communication measurements of CsPbBr3 PQDs all exhibit concentration dependence, suggesting that there exists an optimum concentration to take advantages of performance merits. CsPbBr3 PQDs with a concentration of 0.5 mg/ml show the shortest carrier lifetime and achieve the highest -3 dB bandwidth (168.03 MHz) as well as the highest data rate (660 Mbps) comparing to other concentrations. And in terms of the optimal concentration, we further explored the approach to improve the communication performance, investigating the effect of polarity solvent on the communication performance of CsPbBr3 PQDs. Original 0.5 mg/ml CsPbBr3 PQDs (1 ml) with 55 µL ethanol added in obtain a higher -3 dB bandwidth of 363.68 MHz improved by ∼116.4% and a record data rate of 1.25 Gbps improved by ∼89.4% but weaker PL emission due to energy transfer. The energy transfer assisted improvement may open up a promising avenue to improve the communication performance of QDs, but more feasible energy transfer path needs to be explored to ensure the stability of QDs.

10-Gbps visible light communication in a 10-m free space based on violet series-biased micro-LED array and distance adaptive pre-equalization.

In this paper, we fabricated a 3×3 violet series-biased micro-LED array with high-output optical power and applied it in high-speed and long-distance visible light communication. By employing the orthogonal frequency division multiplexing modulation scheme, distance adaptive pre-equalization, and a bit-loading algorithm, record data rates of 10.23 Gbps, 10.10 Gbps, and 9.51 Gbps were achieved at 0.2 m, 1 m, and 10 m, respectively, below the forward error correction limit of 3.8×10-3. To the best of our knowledge, these are the highest data rates achieved by violet micro-LEDs in free space and the first communication demonstration beyond 9.5 Gbps at 10 m using micro-LEDs.

InGaN micro-LED array with integrated emission and detection functions for color detection application.

InGaN-based micro-LEDs can detect and emit optical signals simultaneously, owing to their overlapping emission and absorption spectra, enabling color detection. In this paper, we fabricated a green InGaN-based micro-LED array with integrated emission and detection functions. On the back side of the integrated device, when the 80 µm micro-LED emitted light, the 200 µm LED could receive reflected light to accomplish color detection. The spacing between the 80 µm and the 200 µm micro-LEDs was optimized to be 1 mm to reduce the effect of the direct light transmitted through the n-GaN layer without reflection. The integrated device shows good detection performance for different colors and skin colors, even in a dark environment. In addition, light can be emitted from the top side of the device. Utilization of light from both sides of the integrated device provides the possibility of its application in display, communication, and detection on the different sides.

Size-dependent sidewall defect effect of GaN blue micro-LEDs by photoluminescence and fluorescence lifetime imaging.

Sidewall defects play a key role in determining the efficiency of GaN-based micro-light emitting diodes (LEDs) for next generation display applications, but there still lacks direct observation of defects-related recombination at the affected area. In this Letter, we proposed a direct technique to investigate the recombination mechanism and size effect of sidewall defects for GaN blue micro-LEDs. The results show that mesa etching will produce stress release near the sidewall, which can reduce the quantum confinement Stark effect (QCSE) to improve the radiative recombination. Meanwhile, the defect-related non-radiative recombination generated by the sidewall defects plays a leading role under low-power injection. In addition, the effective area of the mesas affected by the sidewall defects can be directly observed according to the fluorescence lifetime imaging microscope (FLIM) characterization. For example, the effective area of the mesa with 80 µm is affected by 23% while the entire area of the mesa with 10 µm is almost all affected. This study provides guidance for the analysis and repair of sidewall defects to improve the quantum efficiency of micro-LEDs display at low current density.

Potential influence of fine aerosol chemistry on the optical properties in a semi-arid region.

The current understanding regarding the potential influence of aerosol chemistry on the optical properties does not satisfy accurate evaluation of aerosol radiative effects and precise determination of aerosol sources. We conducted a comprehensive study of the potential influence of aerosol chemistry on the optical properties in a semi-arid region based on various observations. Organic matter was the main contributor to the scattering coefficients followed by secondary inorganic aerosols in all seasons. We further related aerosol absorption to elemental carbon, organic matter, and mineral dust. Results showed that organic matter and mineral dust contributed to >40% of the aerosol absorption in the ultraviolet wavelengths. Therefore, it is necessary to consider the absorption of organic matter and mineral dust in addition to that of elemental carbon. We further investigated the potential influence of chemical composition, especially of organic matter and mineral dust on the optical parameters. Mineral dust contributed to higher absorption efficiency and lower scattering efficiency in winter. The absorption Ångström exponent (AAE) was mostly sensitive to organic matter and mineral dust in winter and spring, respectively; it was relatively high (i.e., 1.68) in winter and moderate (i.e., 1.42) in spring. Unlike in the other seasons, mineral dust contributed to higher mass absorption efficiency in winter. This work reveals the complexity of the relationship between aerosol chemistry and optical properties, and especially the influence of organic matter and mineral dust on aerosol absorption. The results are highly important regarding both regional air pollution and climate.

Cotranslational folding cooperativity of contiguous domains of α-spectrin.

Proteins synthesized in the cell can begin to fold during translation before the entire polypeptide has been produced, which may be particularly relevant to the folding of multidomain proteins. Here, we study the cotranslational folding of adjacent domains from the cytoskeletal protein α-spectrin using force profile analysis (FPA). Specifically, we investigate how the cotranslational folding behavior of the R15 and R16 domains are affected by their neighboring R14 and R16, and R15 and R17 domains, respectively. Our results show that the domains impact each other's folding in distinct ways that may be important for the efficient assembly of α-spectrin, and may reduce its dependence on chaperones. Furthermore, we directly relate the experimentally observed yield of full-length protein in the FPA assay to the force exerted by the folding protein in piconewtons. By combining pulse-chase experiments to measure the rate at which the arrested protein is converted into full-length protein with a Bell model of force-induced rupture, we estimate that the R16 domain exerts a maximal force on the nascent chain of ∼15 pN during cotranslational folding.

Vertical stack integration of blue and yellow InGaN micro-LED arrays for display and wavelength division multiplexing visible light communication applications.

In this work, we demonstrated a convenient and reliable method to realize the vertical stack integration of the blue and yellow InGaN micro-LED arrays. The standard white and color-tunable micro-light sources can be achieved by adjusting the current densities injection of the micro-LEDs. The spectra cover violet, standard white, cyan, etc., showing an excellent color-tunable property. And the mixed standard white light can be separated into red-green-blue three primary colors through the color filters to realize full-color micro-LED display with a color gamut of 75% NTSC. Besides, the communication capability of the integrated micro-LED arrays as visible light communication (VLC) transmitters is demonstrated with a maximum total data rate of 2.35 Gbps in the wavelength division multiplexing (WDM) experimental set-up using orthogonal frequency division multiplexing modulation. In addition, a data rate of 250 Mbps is also realized with the standard white light using on-off keying (OOK) modulation. This integrated device shows great potential in full-color micro-LED display, color-tunable micro-light sources, and high-speed WDM VLC multifunctional applications.

All-fiber LP01-LP11 ultra-broadband mode converters based on T-superimposed long period gratings in PCF.

In order to cover the bandwidth of optical fiber communication, a LP01-LP11 ultra-broadband mode converter based on triple superimposed long period grating in PCF is proposed and demonstrated. The transmission spectra of the D-SLPG with gratings pitches and the T-SLPG were simulated and analyzed. The simulation results on the D-SLPG indicate that the 3 dB bandwidth of the D-SLPG is more than 1.5 times than the 3 dB bandwidth of the independent LPG and the 3 dB bandwidth of T-SLPG approaches 2.6 times as much as the independent LPG. In the experiment, the mode converter based on PCF-T-SLPG covers the wavelength of S + C + L with 3 dB bandwidth of 121 nm from 1498 nm to 1619 nm. In addition, the mode converter based on PCF-T-SLPG can accomplish ultra-broadband transmission in any wavelength by adjusting the period of gratings.

Red, green and blue InGaN micro-LEDs for display application: temperature and current density effects.

Micro-LED has attracted tremendous attention as next-generation display, but InGaN red-green-blue (RGB) based high-efficiency micro-LEDs, especially red InGaN micro-LED, face significant challenges and the optoelectronic performance is inevitably affected by environmental factors such as varying temperature and operating current density. Here, we demonstrated the RGB InGaN micro-LEDs, and investigated the effects of temperature and current density for the InGaN RGB micro-LED display. We found that temperature increase can lead to the changes of electrical characteristics, the shifts in electroluminescence spectra, the increase of full width at half maximum and the decreases of light output power, external quantum efficiency, power efficiency, and ambient contrast ratios, while current density increase can also give rise to different changing trends of the varieties of parameters mentioned just above for the RGB micro-LED display, creating great challenges for its application in practical scenarios. Despite of the varying electrical and optical charateristics, relatively high and stable colour gamut of the RGB display can be maintained under changing temperature and current density. Based on the results above, mechanisms on the temperature and current density effects were analyzed in detail, which would be helpful to predict the parameters change of micro-LED display caused by temperature and current density, and provided guidance for improving the performance of InGaN micro-LED display in the future.

Beyond 25 Gbps optical wireless communication using wavelength division multiplexed LEDs and micro-LEDs.

In this Letter, high-speed optical wireless communication (OWC) with three light-emitting diodes (LED) and five micro-LEDs (µLEDs) is proposed as a proof-of-concept wavelength division multiplexing (WDM) system. It covers a wide spectrum from deep ultraviolet (UV) to visible light and thus could offer both visible light communication (VLC) and UV communication simultaneously. An aggregated data rate of up to 25.20 Gbps over 25 cm free space is achieved, which, to the best of our knowledge, is the highest data rate for LED-based OWC ever reported. Among them, the five µLEDs offer a data rate of up to 18.43 Gbps, which, to the best of our knowledge, is the highest data rate for µLED-based OWC so far. It shows the superiority and potential of µLEDs for WDM-OWC. Additionally, a data rate of 20.11 Gbps for VLC is achieved.

High bandwidth series-biased green micro-LED array toward 6 Gbps visible light communication.

In this Letter, a record modulation bandwidth of 1.31 GHz was achieved by a 10 µm c-plane green micro light emitting diode (micro-LED) at a current density of 41.4 kA/cm2. Furthermore, by designing a series-biased 20 µm micro-LED with higher light output power, combined with an orthogonal frequency division multiplexing modulation scheme, a maximum data rate of 5.789 Gbps was achieved at a free-space transmission distance of 0.5 m. This work demonstrates the prospect of c-plane polar green micro-LED in ultrahigh-speed visible light communication, which is expected to realize a high-performance wireless system in the future.

A prognostic nomogram based on a new classification of combined micropapillary and solid components for stage IA invasive lung adenocarcinoma.

BACKGROUND: We aimed to develop a prognostic nomogram based on a new classification of combined micropapillary and solid components in pathological stage IA invasive lung adenocarcinoma (LUAD). METHODS: According to the total proportion of solid and micropapillary components (TPSM), the X-tile software was applied to classify patients into the following three groups: TPSM-low (TPSM-L), TPSM-middle (TPSM-M), and TPSM-high (TPSM-H). The postoperative survival was compared among the three groups. The multivariate Cox regression analysis was performed to identify independent prognostic factors for survival. According to these factors, a nomogram model was developed to provide a personalized prognostic evaluation. RESULTS: A total of 595 patients with pathological stage IA invasive LUAD were included in our study. The 5-year disease-free survival and overall survival rates in patients with TPSM-H and TPSM-M were significantly lower than those with TPSM-L. The multivariate Cox regression analysis revealed that the TPSM classification was an independent prognostic factor for survival. According to TPSM classification, we developed a nomogram model which had good calibration and reliable discrimination ability to evaluate survival. CONCLUSIONS: The nomogram based on the combination of micropapillary and solid components has good prognostic value in predicting postoperative recurrence and survival of patients with pathological stage IA invasive LUAD.

Chemical characteristics and regional transport of submicron particulate matter at a suburban site near Lanzhou, China.

Lanzhou, which is a valley city on the Loess Plateau, frequently suffered from aerosol pollution in recent years, especially in winter. However, the lack of understanding of factors governing aerosol pollution limits the implementation of effective emission policies in and around Lanzhou. To help solve this problem, an intensive field campaign was conducted at the SACOL site, which is a suburban site near Lanzhou, in winter 2018. The chemical characteristics and sources of submicron particulate matter (PM1) were investigated, and the influence of the topography around Lanzhou on aerosol pollution was examined. In the present study, the average PM1 mass concentration reached 25.6 ± 12.8 µg m-3, with 41.0% organics, 16.1% sulfate, 19.7% nitrate, 10.7% ammonium, 3.1% chloride, and 9.4% black carbon (BC). Three organic aerosol (OA) factors were identified with the positive matrix factorization (PMF) algorithm, including a biomass burning OA (BBOA, 13.6%), a coal combustion OA (CCOA, 34.2%), and an oxygenated OA (OOA, 52.2%). The significant relationships between organics, BC, and chloride and wind pattern suggested that the SACOL site was strongly influenced by regionally transported aerosols. Further analysis suggested that these aerosol regional transport events were caused by topography. Due to the limitation of the valley, aerosols accumulated in the valley. These accumulated aerosols were then transported to the SACOL site along the valley by prevailing winds. Our study highlights enhanced aerosol regional transport in valleys, which provides a new perspective for future studies on aerosol pollution in basins and valleys.

Changes in physical and chemical properties of urban atmospheric aerosols and ozone during the COVID-19 lockdown in a semi-arid region.

The synergistic response of urban atmospheric aerosols and ozone (O3) to reduction of anthropogenic emissions is complicated and still needs further study. Thus, the changes in physical and chemical properties of urban atmospheric aerosols and O3 during the Coronavirus Disease 2019 (COVID-19) lockdown were investigated at three urban sites and one rural site in Lanzhou with semi-arid climate. Fine particulate matter (PM2.5) decreased at four sites by âˆ¼ 20% while O3 increased by >100% at two urban sites during the COVID-19 lockdown. Both primary emissions and secondary formation of PM2.5 decreased during the lockdown. Significant increase in both sulfur and nitrogen oxidation ratios was found in the afternoon, which accounted for 48.7% of the total sulfate and 40.4% of the total nitrate, respectively. The positive matrix factorization source apportionment revealed increased contribution of secondary formation and decreased contribution of vehicle emissions. Aerosol scattering and absorption decreased by 33.6% and 45.3%, resulting in an increase in visibility by 30% and single scattering albedo (SSA) at 520 nm slightly increased by 0.02. The enhanced O3 production was explained by increased volatile organic compounds to nitrogen oxides ratio, decreased aerosol, as well as increased SSA. The primary emissions of secondary aerosol precursors significantly decreased while Ox (i.e., NO2 and O3) exhibited little change. Consequently, Ox to CO ratio, PM2.5 to elemental carbon (EC) ratio, secondary inorganic aerosols to EC ratio, and secondary organic carbon to EC ratio increased, confirming enhanced secondary aerosol production efficiency during the lockdown. Positive feedback among O3 concentration, secondary aerosol formation, and SSA was revealed to further promote O3 production and secondary aerosol formation. These results provide scientific guidance for collaborative management of O3 and particulate matter pollution for cities with semi-arid climate.

Prognostic significance of 4R lymph node dissection in patients with right primary non-small cell lung cancer.

BACKGROUND: To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection. RESULTS: Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD- group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD- group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08-1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04-1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002). CONCLUSIONS: Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.

Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model.

Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.

Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.