Miracle-dz/UniFAR-FTUs huggingface dataset:
Subfunctionalization of Paralog Transcription Factors Contributes to Regulation of Alkaloid Pathway Branch Choice in Catharanthus roseus

Catharanthus roseus produces a diverse range of specialized metabolites of the monoterpenoid indole alkaloid (MIA) class in a heavily branched pathway. Recent great progress in identification of MIA biosynthesis genes revealed that the different pathway branch genes are expressed in a highly cell type- and organ-specific and stress-dependent manner. This implies a complex control by specific transcription factors (TFs), only partly revealed today. We generated and mined a comprehensive compendium of publicly available C. roseus transcriptome data for MIA pathway branch-specific TFs. Functional analysis was performed through extensive comparative gene expression analysis and profiling of over 40 MIA metabolites in the C. roseus flower petal expression system. We identified additional members of the known BIS and ORCA regulators. Further detailed study of the ORCA TFs suggests subfunctionalization of ORCA paralogs in terms of target gene-specific regulation and synergistic activity with the central jasmonate response regulator MYC2. Moreover, we identified specific amino acid residues within the ORCA DNA-binding domains that contribute to the differential regulation of some MIA pathway branches. Our results advance our understanding of TF paralog specificity for which, despite the common occurrence of closely related paralogs in many species, comparative studies are scarce. SIGNIFICANCE STATEMENT A gene discovery program for regulators of monoterpenoid indole alkaloid biosynthesis in Catharanthus roseus advances our understanding of paralog specificity and subfunctionalization of the renowned class of ORCA transcription factors, particularly in terms of target gene-specificity and synergistic activity with other jasmonate-responsive transcription factors.
Analysis of solid state phase transformation kinetics: models and recipes

The progress of solid-state phase transformations can generally be subdivided into three overlapping mechanisms: nucleation, growth and impingement. These can be modelled separately if hard impingement prevails. On that basis, an overview has been given of recent numerical and analytical methods for determination of the kinetic parameters of a transformation. The treatment focuses on both isothermally and isochronally conducted transformations. To extend the range of transformations that can be described analytically, a number of more or less empirical submodels, which are compatible with experimental results, has been included in the discussion. It has been shown that powerful, flexible, analytical models are possible, once the concept of time or temperature dependent growth exponent and effective activation energy, in agreement with the existing experimental observations, has been adopted. An explicit (numerical) procedure to deduce the operating kinetic processes from experimental transformation-rate data, on the basis of different nucleation, growth and hard impingement mechanisms, has been demonstrated. Without recourse to any specific kinetic model, simple recipes have been given for the determination of the growth exponent and the effective activation energy from the experimental transformation-rate data.
Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli

Environmental cues in an ecological niche are temporal. In response to these temporal cues, bacteria have been known to exhibit learning or conditioning, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature in the regulatory networks in microorganisms. However, the conditions under which an anticipatory response optimizes cellular fitness are not known. Nor has evolution of anticipatory regulation in laboratory conditions been experimentally demonstrated. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and present the key variables in cellular physiology associated with response to the cues whose modulation is likely to lead to evolution of anticipatory regulatory response. We predict experimental conditions, which are likely to lead to demonstration of rewiring of regulation, and evolution of anticipatory response in bacterial populations. Using inputs from the modeling results, we evolve E. coli in alternating environments of the pentose sugar rhamnose and paraquat, which induces oxidative stress. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. Thus, we argue that in niches where environmental stimuli have a cyclical nature, conditioning evolves in a population as an adaptive response.
WORKING PAPER SERIES HOW DO CEOS MAKE STRATEGY ?

We explore the critical question of how executives make strategic decisions. Utilizing a new survey of 262 CEO alumni of Harvard Business School, we gather evidence on four aspects of each executive’s business strategy: its overall structure, its formalization, its development, and its implementation. We report three key results. First, different CEOs use markedly different processes to make strategic decisions; some follow highly formalized, rigorous, and deliberate processes, while others rely heavily on instinct and intuition. Second, more structured strategy processes are associated with larger firm size and faster employment growth. Third, using a regression discontinuity centered around a change in the curriculum of Harvard Business School’s required strategy course, we trace differences in strategic decision making back to differences in managerial education. Mu-Jeung Yang David Eccles School of Business Salt Lake City, UT mjyang@eccles.utah. edu Michael Christensen Harvard Business School Soldiers Field Boston, MA 02163 mchristensen@hbs.edu Nicholas Bloom Stanford University Department of Economics 579 Serra Mall Stanford, CA 94305-6072 and NBER nbloom@stanford.edu Raffaella Sadun Harvard Business School Morgan Hall 233 Soldiers Field Boston, MA 02163 and NBER rsadun@hbs.edu Jan Rivkin Harvard Business School Morgan Hall Boston, MA 02163 jrivkin@hbs.edu
UISP 2017 Proceedings of the Workshop on User Interfaces and Scheduling and Planning

Pilots have benefited from ever-increasing and evolving automation techniques for many decades. This automation has allowed pilots to handle increasingly complex aircraft with greater safety, precision, and reduced workload. Unfortunately, it can also lead to misunderstandings and loss of situational awareness. In the face of malfunctions or unexpected events, pilots sometimes have an unclear picture of the situation and what to do next, or must find and follow written procedures that do not take into account all the details of the particular situation. Pilots may also incorrectly assume the mode or state of an automated system and fail to perform certain necessary actions that they assumed an automated system would handle. To help alleviate these issues, we introduce the Cockpit Hierarchical Activity Planning and Execution (CHAP-E) system. CHAP-E provides pilots with guidance toward executing procedures based on the aircraft and automation system’s state and assists pilots through both nominal and off-nominal flight situations.
Early Improvement of Acute Respiratory Distress Syndrome in Patients with COVID-19: Insights from the Data of ICU Patients in Chongqing, China

Acute respiratory distress syndrome (ARDS) may be the main cause of death in patients with coronavirus disease 2019 (COVID-19). Herein, we retrospect clinical features, outcomes and ARDS characteristics of 75 intensive care unit (ICU) patients with COVID-19 in Chongqing, China. We found a 5.3% case fatality rate of the ICU patients in Chongqing. 93% patients developed ARDS during the intensive care, and more than half were moderate. However, most of the patients (55%) supported with high flow nasal cannula (HFNC) oxygen therapy, but not mechanical ventilation. Nearly one third of patients with ARDS got an early improvement (eiARDS), and the rate is much higher than the other causes of ARDS in a previous study. Patients with eiARDS had a higher survival rate and lower length of ICU stay. The age (< 55 years) is an independent predictor for the eiARDS, and stratification of COVID-19 patients by age is recommended.
Synthetic Biology and Biocomputational Approaches for Improving Microbial Endoglucanases toward Their Innovative Applications

Microbial endoglucanases belonging to the β-1–4 glycosyl hydrolase family are useful enzymes due to their vast industrial applications in pulp and paper industries and biorefinery. They convert lignocellulosic substrates to soluble sugars and help in the biodegradation process. Various biocomputational tools can be utilized to understand the catalytic activity, reaction kinetics, complexity of active sites, and chemical behavior of enzyme complexes in reactions. This might be helpful in increasing productivity and cost reduction in industries. The present review gives an overview of some interesting aspects of enzyme design, including computational techniques such as molecular dynamics simulation, homology modeling, mutational analysis, etc., toward enhancing the quality of these enzymes. Moreover, the review also covers the aspects of synthetic biology, which could be helpful in faster and reliable development of useful enzymes with desired characteristics and applications. Finally, the review also deciphers the utilization of endoglucanases in biodegradation and emphasizes the use of diversified protein engineering tools and the modification of metabolic pathways for enzyme engineering.
Factors for incidence risk and prognosis in non-small-cell lung cancer patients with synchronous brain metastasis: a population-based study.

Background: We aimed to investigate the epidemiology of synchronous brain metastasis (SBM) in non-small-cell lung cancer (NSCLC) patients. Methods: Logistic regression and Cox regression were used to identify the related factors of SBM incidence and cancer-specific survival (CSS). A nomogram for predicting CSS was developed and validated. Results: The incidence of SBM in NSCLC patients was 12.58%. The median CSS was 5 months. Patients with younger age, female gender, and adenocarcinoma had higher odd ratios for developing SBM. In addition, a nomogram was developed based on significant factors from Cox regression. The validation of the nomogram showed that it had good calibration and discrimination. Conclusions: SBM was highly prevalent in NSCLC patients, who also had poor survival.
Rickettsia-host interaction: strategies of intracytosolic host colonization

ABSTRACT Bacterial infection is a highly complex biological process involving a dynamic interaction between the invading microorganism and the host. Specifically, intracellular pathogens seize control over the host cellular processes including membrane dynamics, actin cytoskeleton, phosphoinositide metabolism, intracellular trafficking and immune defense mechanisms to promote their host colonization. To accomplish such challenging tasks, virulent bacteria deploy unique species-specific secreted effectors to evade and/or subvert cellular defense surveillance mechanisms to establish a replication niche. However, despite superficially similar infection strategies, diverse Rickettsia species utilize different effector repertoires to promote host colonization. This review will discuss our current understandings on how different Rickettsia species deploy their effector arsenal to manipulate host cellular processes to promote their intracytosolic life within the mammalian host.
The effect of effort-reward imbalance on brain structure and resting-state functional connectivity in individuals with high levels of schizotypal traits

ABSTRACT Introduction Effort-reward imbalance (ERI) is a typical psychosocial stress. Schizotypal traits are attenuated features of schizophrenia in the general population. According to the diathesis-stress model, schizotypal traits and psychosocial stress contribute to the onset of schizophrenia. However, few studies examined the effects of these factors on brain alterations. This study aimed to examine relationships between ERI, schizotypal traits and brain structures and functions. Methods We recruited 37 (13 male, 24 female) participants with high levels of schizotypal traits and 36 (12 male, 24 female) participants with low levels of schizotypal traits by the Schizotypal Personality Questionnaire (SPQ). The Chinese school version of the effort-reward imbalance questionnaire (C-ERI-S) was used to measure ERI. We conducted the voxel-based morphometry (VBM) and whole brain resting-state functional connectivity (rsFC) analysis using reward or stress-related regions as seeds. Results Participants with high levels of schizotypal traits were more likely to perceive ERI. The severity of ERI was correlated with grey matter volume (GMV) reduction of the left pallidum and altered rsFC among the prefrontal, striatum and cerebellum in participants with high levels of schizotypal traits. Conclusion ERI is associated with GMV reduction and altered rsFC in individuals with high levels of schizotypal traits.
Host versus cell-dependent effects of β-Arrestin-1 expression in prostate tumorigenesis.

Prostate cancer constitutes a serious health challenge and remains one of the main causes of cancer-related death among men. The more aggressive form of the disease has been attributed to androgen independence; resulting in lack of response to androgen deprivation therapy and sustained activation of other growth pathways. The scaffold proteins β-arrestin 1 and 2 (βarr1 and βarr2) which are known to mediate G protein-coupled receptor desensitization and internalization, were also shown to modulate prostate tumorigenesis. βarr1 is significantly overexpressed (>4 fold) in prostate cancer cells relative to βarr2. In this study, we investigated the effect of βarr1 overexpression in prostate cancer development and progression using the mouse and human PCa cell xenografts, and autochthonous transgenic adenocarcinoma mouse prostate (TRAMP) models deficient in β-arrestins Depletion of βarr1 in TRAMP mice (TRAMP/βarr1 -/-) increased PCa growth and decreased overall survival relative to control TRAMP or TRAMP/βarr2 -/- animals. Prostate tissues from TRAMP/βarr1 -/- tumors displayed an increase in androgen receptor expression whereas overexpression of βarr1 in TRAMP-C1 (TRAMP-C1-βarr1-GFP) which derived from TRAMP decreased AR expression, cell proliferation and tumor growth in nude mice xenografts, relative to control TRAMP-C1-GFP. Knockdown of βarr1 expression in human MDA PCa 2b cells (MDA PCa 2b-βarr1 -/-) also decreased AR expression cell proliferation and tumor growth relative to control (MDA PCa 2b-Sham) cells. Interestingly, both TRAMP-C1-βarr1-GFP and MDA PCa 2b-βarr1 -/- xenografts showed a decrease in AKT phosphorylation, but an increase MAPK activation. Altogether, the data indicate that the effect of βarr1 in modulating AR signaling to regulate prostate cancer aggressiveness is cell and host autonomous.
The clinical features, management, and survival of elderly patients with colorectal cancer.

Background As the population ages, the number of elderly patients with colorectal cancer is increasing year by year. However, older people have rarely been the focus of studies on colorectal cancer. Therefore, in the present study, we aimed to carry out a retrospective analysis of this patient subgroup. Methods A retrospective study of clinical data of patients aged over 80 years who died from colorectal cancer in our hospital between 1993 and 2020 was performed. Logistic regression, the Kaplan-Meier method, and a multivariate Cox proportional hazards model were used to analyze the overall survival and treatment outcomes of the patients. Results A total of 87 patients were included in the study. The overall median survival was 45 months. In most patients, the primary lesion was located in the right colon. One-quarter of the patients refused to accept any treatment. Patients with stage IV tumors, who accounted for the largest proportion of the study population, displayed a higher rate of abandoning treatment than did patients of other stages. Almost all patients with stages II and III accepted surgery. Patients who underwent surgery to treat their colorectal cancer had longer survival than those who did not. Conclusions Old age should not be a reason for giving up treatment for colorectal cancer. The treatment of colorectal cancer patients aged 80 years and above requires individualized evaluation and more aggressive treatment to achieve greater benefits.
Optimizing Nasal Reconstruction in Severe Congenital Nasal Deviations

Abstract Nasal deviations pose a 2-fold task for plastic surgeons, as the correction must often address both functional and aesthetic challenges. Regardless of the etiology of the nasal deviation, the principles of treatment have been previously extensively described. The authors present an extreme case of congenital nasal deviation in an 18-year-old male acquired as a result of abnormal in-utero positioning during a multigestational pregnancy. Through this case, the authors demonstrate effective use of previously described surgical principles in treating a severe congenital nasal deviation and reinforce the importance of postoperative nasal manipulation to maintain the desired outcome.
Cochlear Duct Length Calculation: Comparison Between Using Otoplan and Curved Multiplanar Reconstruction in Nonmalformed Cochlea

Objective: To describe a new method to measure the cochlear parameters using Otoplan software, and to compare it with the traditional method using curved multiplanar reconstruction (cMPR). Study Design: Retrospective analysis using internal consistency reliability and paired sample t test. Setting: Tertiary referral center. Patients: Thirty-four patients including 68 ears from a clinical trial were retrospectively reviewed. Main Outcome Measures: The length, width, height (distances A, B, H), and cochlear duct length of each cochlea were measured independently using two modalities: Otoplan and cMPR. Internal consistency reliability of the two modalities was analyzed. The time spent on each measurement was also recorded. Results: Otoplan software was compatible with all radiological data in this series. Distances A, B, and H showed no significant differences between Otoplan (9.33 ± 0.365, 6.61 ± 0.359, and 2.91 ± 0.312 mm) and cMPR (9.32 ± 0.314, 6.59 ± 0.342, and 2.93 ± 0.250 mm). The average cochlear duct length calculated by Otoplan was 34.37 ± 1.481 mm, which was not significantly different from that calculated by cMPR (34.55 ± 1.903mm, p = 0.215). The measurements with Otoplan had better internal consistency reliability compared with those by cMPR, and measurements with a higher peak kilovoltage (140 kVp) CT scan showed further higher internal consistency reliability. Time spent on each cochlea by Otoplan was 5.9 ± 0.69 min, significantly shorter than that by cMPR (9.3 ± 0.72 min). Conclusion: Otoplan provides more rapid and reliable measurement of the cochlea than cMPR. Furthermore, it can be easily used in the laptop computer.
Uptake of oxo-anions by cements through solid-solution formation: experimental evidence and modelling

Summary Uptake experiments were carried out with selenate and chromate on fresh and leached Portland and high-alumina cements; and in addition with selenate and selenite on synthetic ettringite. In all experiments with cements, exceptionally high uptake could be observed under conditions where significant amounts of secondary ettringite were formed. Experimental data obtained for pure ettringite corroborated the important role of this mineral phase. However, uptake kinetics show opposite trends in these two systems, which can be viewed as end-members of the same process: Where a fast precipitation of secondary ettringite occurred, initial uptake was high, with Kd values in the range of ≍1-5 m3/kg for Se(VI), but decreased with time. Uptake by pre-formed (primary) ettringite initially gave lower Kd values (≍0.1 m3/kg), which increased with time. After prolonged equilibration times, the two systems started to approach each other. Concurrent measurements of sulphate concentrations allowed to extract a mean partition coefficient for the solid-solution formation of selenite and selenate with ettringite. Based on this simple solid-solution model, a pragmatic quantitative relation was developed that permits to estimate Kd for Se(VI) on whole cement as a function of the concentrations of sulphate in the cement and in the solution. A test against experimental data shows reasonably good agreement between measurements and calculations. This relation can also be directly applied to estimate Kd values of chromate (and perrhenate) by different cements, indicating the same uptake mechanism. The approach may be less well suited for Se(IV), whose uptake on cement appears to be related mainly to minerals other than ettringite.
Temperature sensitivity of SOM decomposition is linked with a K‐selected microbial community

Temperature sensitivity (Q10) of soil organic matter (SOM) decomposition is a crucial parameter to predict the fate of soil carbon (C) under global warming. Nonetheless, the response pattern of Q10 to continuous warming and the underlying mechanisms are still under debate, especially considering the complex interactions between Q10, SOM quality, and soil microorganisms. We examined the Q10 of SOM decomposition across a mean annual temperature (MAT) gradient from −1.9 to 5.1°C in temperate mixed forest ecosystems in parallel with SOM quality and bioavailability, microbial taxonomic composition, and functional genes responsible for organic carbon decomposition. Within this temperature gradient of 7.0°C, the Q10 values increased with MAT, but decreased with SOM bioavailability. The Q10 values increased with the prevalence of K‐strategy of soil microbial community, which was characterized by: (i) high ratios of oligotrophic to copiotrophic taxa, (ii) ectomycorrhizal to saprotrophic fungi, (iii) functional genes responsible for degradation of recalcitrant to that of labile C, and (iv) low average 16S rRNA operon copy number. Because the recalcitrant organic matter was mainly utilized by the K‐strategists, these findings independently support the carbon quality‐temperature theory from the perspective of microbial taxonomic composition and functions. A year‐long incubation experiment was performed to determine the response of labile and recalcitrant C pools to warming based on the two‐pool model. The decomposition of recalcitrant SOM was more sensitive to increased temperature in southern warm regions, which might attribute to the dominance of K‐selected microbial communities. It implies that climate warming would mobilize the larger recalcitrant pools in warm regions, exacerbating the positive feedback between increased MAT and CO2 efflux. This is the first attempt to link temperature sensitivity of SOM decomposition with microbial eco‐strategies by incorporating the genetic information and disentangling the complex relationship between Q10 and soil microorganisms.