Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic ...information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA. An analysis of microsatellite instable (MSI) cell lines reveals the dysregulation of specific protein complexes associated with surveillance of mutation and translation. These and other protein complexes were associated with sensitivity to knockdown of several different genes. These data in conjunction with the wider CCLE are a broad resource to explore cellular behavior and facilitate cancer research.
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•Quantified the proteomes of 375 cell lines from diverse lineages in the CCLE•Correlated expression of proteins across many pathways•Downregulation of multiple protein complexes in microsatellite instability•Protein complexes associated with sensitivity to gene knockdown and mutation
Quantitative proteomes of 375 cancer cell lines for the Cancer Cell Line Encyclopedia (CCLE) reveal correlated protein expression between multiple pathways and complexes as well as associations between protein complexes and genetic features including microsatellite instability, individual gene mutations, and sensitivity to gene knockdowns.
Regular consumption of fermented dairy products helps maintain a healthy microbiota and prevent gut dysbiosis-linked diseases. The lactic acid bacteria (LAB) present in food enhance the digestibility ...of proteins, moderate the release of fatty acids, and support human health through inhabiting the gastrointestinal tract. These desirable properties of LAB are attributed, in part, to their metabolic processes involving enzymes such as lipases, proteases, and antibacterial proteins. The LAB strains presenting higher enzymatic activities may offer improved functionality for applications in foods. The first aim of this work was to isolate and identify LAB from diverse dairy products and select those with enhanced enzymatic activities. Secondly, this work aimed to investigate the subcellular organization and identity of these enzymes after semi-purification. Out of the total 137 LAB strains isolated and screened, 50.3% and 61.3% of the strains exhibited lipolytic and proteolytic activities, respectively. Seven strains displaying high enzymatic activities were selected and further characterized for the cellular organization of their lipases, proteases, and antibacterial proteins. The lipolytic and proteolytic activities were exhibited predominantly in the extracellular fraction; whereas, the antibacterial activities were found in various cellular fractions and were capable of inhibiting common undesirable microorganisms in foods. In total, two lipases, seven proteases, and three antibacterial proteins were identified by LC-MS/MS. Characterization of LAB strains with high enzymatic activity has potential biotechnological significance in fermentative processes and in human health as they may improve the physicochemical characteristics of foods and displace strains with weaker enzymatic activities in the human gut microbiota.
Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino ...acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
We present an analysis of hydrodynamic effects in systems involving ion transport from an aqueous electrolyte to an ion‐selective surface. These systems are described by the Poisson–Nernst–Planck and ...Navier–Stokes equations. Historically, such systems were modeled by one‐dimensional geometries with spatial coordinate in the direction of transport and normal to the ion‐selective surface. Rubinstein and Zaltzman JFM 579, 173–226 (2007) showed that when such systems are unbounded in the transverse directions, a hydrodynamic instability can occur. This instability, referred to as electroconvective instability, leads to advective mixing, which results in overlimiting transport rates significantly beyond what is predicted from one‐dimensional models. In this study, we present an analysis of electroconvection in confined systems, considering a broad range of applications including microfluidic systems and porous media. Our analysis reveals that full confinement in the transverse directions significantly suppresses electroconvection and overlimiting current. However, when at least one transverse direction allows for flow escape, such as in thin but wide channels or in porous media, the onset of instability is only weakly affected by confinement. We will also present a review of relevant literature and discuss how the present study resolves the contradictory contrasts between the results of recent work on this topic.
To describe a technique for contained power morcellation within an insufflated isolation bag at the time of uterine specimen removal during minimally invasive gynecologic procedures.
Over the study ...period of January 2013 to April 2014, 73 patients underwent morcellation of the uterus or myomas within an insufflated isolation bag at the time of minimally invasive hysterectomy or myomectomy. This technique involves placing the specimen into a large plastic bag within the abdomen, exteriorizing the opening of the bag, insufflating the bag within the peritoneal cavity, and then using a power morcellator within the bag to remove the specimen in a contained fashion. Procedures were performed at four institutions and included multiport laparoscopy, single-site laparoscopy, multiport robot-assisted laparoscopy, or single-site robot-assisted laparoscopy. Demographic and perioperative characteristics were collected for the cases.
Surgical specimen morcellation within an insufflated isolation bag was successfully used in all cases. The median operative time was 114 minutes (range 32-380 minutes), median estimated blood loss was 50 mL (range 10-500 mL), and the median specimen weight was 257 g (range 53-1,481 g). There were no complications related to the contained morcellation technique nor was there visual evidence of tissue dissemination outside of the isolation bag.
Morcellation within an insufflated isolation bag is a feasible technique. Methods for morcellating uterine tissue in a contained manner may provide an option to minimize the risks of open power morcellation while preserving the benefits of minimally invasive surgery.
II.
Neurodivergent students exhibit an inclination towards Science, Technology, Engineering and Mathematics (STEM) fields, yet their learning experiences in STEM courses remain underexamined. Utilizing ...an online survey of neurodivergent (n = 60) and neurotypical (n = 83) US college students, this study identified various factors influencing their self‐perceived learning experiences, including interest in the course content, instruction quality and performance outcomes. Compared to their neurotypical peers, neurodivergent students attributed negative experiences in STEM courses less frequently to performance‐related factors and more often to a mismatch between their interests and the course content. Both groups also articulated a variety of strengths and challenges encountered in their STEM studies. Neurodivergent students were more likely to report having interest and passion for STEM and less likely to report having peer support and effective study skills and habits as their primary strength for studying STEM. Conversely, while neurotypical students cited difficult content as their central challenge, neurodivergent students more commonly faced challenges with focus and attention. Despite the study's limited sample size, it revealed emerging patterns that emphasize the importance of developing inclusive teaching methods and specific support mechanisms to cater to the unique strengths and challenges of neurodivergent students in higher education.
•This study evaluated the efficacy of fractional CO2 laser treatments in gynecologic cancer survivors with GSM.•There were no serious adverse events as a result of laser treatment or sham laser in ...gynecologic cancer survivors .•Fractional CO2 laser treatments appeared to improve sexual function, when compared with sham laser.•This study is the first sham controlled study of fractional CO2 laser treatment in gynecologic cancer survivors.
The objectives of this study were to evaluate the feasibility and efficacy of fractional CO2 laser therapy in gynecologic cancer survivors.
This was a pilot, multi-institutional randomized sham-controlled trial of women with gynecologic cancers with dyspareunia and/or vaginal dryness. Participants were randomized to fractional CO2 laser treatment or sham laser treatment. The primary aim was to estimate the proportion of patients who had improvement in symptoms based on the Vaginal Assessment Scale (VAS). Secondary aims included changes in sexual function assessed using the Female Sexual Functioning Index (FSFI) and urinary symptoms assessed using the the Urinary Distress Inventory (UDI-6).
Eighteen women participated in the study, ten in the treatment arm and eight in the sham arm. The majority of participants had stage I (n = 11, 61.1 %) or II (n = 3, 16.7 %) endometrial cancer with adenocarcinoma histology (n = 9, 50 %). In total, 15 (83.3 %) of the participants completed all treatments and follow-up visit. There was no difference in the change in the median VAS score from baseline to follow-up. However, there was an improvement in change in the median total FSFI score with treatment compared with sham (Δ 6.5 vs −0.3, p = 0.02). The change in the median UDI-6 score was lower in the treatment arm (Δ −14.6 vs −2.1, p = 0.17), but this was not statistically significant. There were no reported serious adverse events.
Fractional CO2 laser therapy is feasible in gynecologic cancer survivors, with preliminary evidence of safety. In addition, there was preliminary evidence of improvement in sexual function compared with sham treatment.
Clinicaltrial.gov Identifier: NCT03372720 (OSU-17261; NCI-2017-02051)
To compare perioperative outcomes, particularly operative time, between uncontained and in-bag power morcellation of uterine tissue at the time of laparoscopic surgery.
Canadian Task Force ...classification II-3.
Academic tertiary care hospitals.
Women undergoing laparoscopic hysterectomy or myomectomy who required morcellation of uterine tissue for specimen extraction.
Outcomes among patients who had in-bag power morcellation were compared with outcomes among patients who had traditional power morcellation. The technique for in-bag morcellation entails placing the specimen into a large containment bag within the abdomen, insufflating the bag within the peritoneal cavity, and then using a power morcellator to remove the specimen from inside the bag.
The cohort consisted of 85 consecutive patients who underwent surgery with morcellation of uterine tissue. Prospective data collected from 36 patients who underwent in-bag morcellation were compared with retrospective data collected from the immediately preceding 49 patients who had uncontained power morcellation. Baseline demographics were comparable between the 2 groups although women who underwent in-bag morcellation were on average older than the open morcellation group (mean age in years standard deviation, 49.19 1.12 vs 44.06 8.93; p = .01). The mean operating room time was longer in the in-bag morcellation group (mean time in minutes standard deviation, 119.0 55.91 vs 93.13 44.90; p = .02). The estimated blood loss, specimen weight, hospital length of stay, and perioperative complication rate did not vary between the 2 groups. Operative times did not vary significantly by surgeon. There were no cases of malignancy or isolation bag disruption.
In-bag power morcellation, a tissue extraction technique developed to reduce the risk of tissue dissemination, results in perioperative outcomes comparable with the traditional laparoscopic approach. In this cohort, the mean operative time was prolonged by 26 minutes with in-bag morcellation but may potentially be reduced with further refinement of the technique.
Hysterectomy (i.e., surgical removal of the uterus) requires severing the main blood supply to the uterus (i.e., the uterine arteries) while preserving the nearby, often overlapping, ureters. In this ...paper, we investigate dual-wavelength and audiovisual photoacoustic imaging-based approaches to visualize and differentiate the ureter from the uterine artery and to provide the real-time information needed to avoid accidental ureteral injuries during hysterectomies. Dual-wavelength 690/750 nm photoacoustic imaging was implemented during laparoscopic and open hysterectomies performed on human cadavers, with a custom display approach designed to visualize the ureter and uterine artery. The proximity of the surgical tool to the ureter was calculated and conveyed by tracking the surgical tool in photoacoustic images and mapping distance to auditory signals. The dual-wavelength display showed up to 10 dB contrast differences between the ureter and uterine artery at three separation distances (i.e., 4 mm, 5 mm, and 6 mm) during the open hysterectomy. During the laparoscopic hysterectomy, the ureter and uterine artery were visualized in the dual-wavelength image with up to 24 dB contrast differences. Distances between the ureter and the surgical tool ranged from 2.47 to 7.31 mm. These results are promising for the introduction of dual-wavelength photoacoustic imaging to differentiate the ureter from the uterine artery, estimate the position of the ureter relative to a surgical tool tip, map photoacoustic-based distance measurements to auditory signals, and ultimately guide hysterectomy procedures to reduce the risk of accidental ureteral injuries.
Technology‐based, open‐ended learning environments (OELEs) can capture detailed information of students' interactions as they work through a task or solve a problem embedded in the environment. This ...information, in the form of log data, has the potential to provide important insights about the practices adopted by students for scientific inquiry and problem solving. How to parse and analyse the log data to reveal evidence of multifaceted constructs like inquiry and problem solving holds the key to making interactive learning environments useful for assessing students' higher‐order competencies. In this paper, we present a systematic review of studies that used log data generated in OELEs to describe, model and assess scientific inquiry and problem solving. We identify and analyse 70 conference proceedings and journal papers published between 2012 and 2021. Our results reveal large variations in OELE and task characteristics, approaches used to extract features from log data and interpretation models used to link features to target constructs. While the educational data mining and learning analytics communities have made progress in leveraging log data to model inquiry and problem solving, multiple barriers still exist to hamper the production of representative, reproducible and generalizable results. Based on the trends identified, we lay out a set of recommendations pertaining to key aspects of the workflow that we believe will help the field develop more systematic approaches to designing and using OELEs for studying how students engage in inquiry and problem‐solving practices.
Practitioner notes
What is already known about this topic
Research has shown that technology‐based, open‐ended learning environments (OELEs) that collect users' interaction data are potentially useful tools for engaging students in practice‐based STEM learning.
More work is needed to identify generalizable principles of how to design OELE tasks to support student learning and how to analyse the log data to assess student performance.
What this paper adds
We identified multiple barriers to the production of sufficiently generalizable and robust results to inform practice, with respect to: (1) the design characteristics of the OELE‐based tasks, (2) the target competencies measured, (3) the approaches and techniques used to extract features from log files and (4) the models used to link features to the competencies.
Based on this analysis, we can provide a series of specific recommendations to inform future research and facilitate the generalizability and interpretability of results:
Making the data available in open‐access repositories, similar to the PISA tasks, for easy access and sharing.
Defining target practices more precisely to better align task design with target practices and to facilitate between‐study comparisons.
More systematic evaluation of OELE and task designs to improve the psychometric properties of OELE‐based measurement tasks and analysis processes.
Focusing more on internal and external validation of both feature generation processes and statistical models, for example with data from different samples or by systematically varying the analysis methods.
Implications for practice and/or policy
Using the framework of evidence‐centered assessment design, we have identified relevant criteria for organizing and evaluating the diverse body of empirical studies on the topic and that policy makers and practitioners can use for their own further examinations.
This paper identifies promising research and development areas on the measurement and assessment of higher‐order constructs with process data from OELE‐based tasks that government agencies and foundations can support.
Researchers, technologists and assessment designers might find useful the insights and recommendations for how OELEs can enhance science assessment through thoughtful integration of learning theories, task design and data mining techniques.
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