Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations That Increase the Life Span of C. elegans Inhibit Tumor Growth

Mutations in gld-1 cause lethal germline tumors in the nematode Caenorhabditis elegans. We find that a wide variety of mutations that extend C. elegans' life span confer resistance to these tumors. The long life spans of daf-2/insulin-receptor mutants were not shortened at all by gld-1 mutations; we attribute this finding to decreased cell division and increased DAF-16/p53–dependent apoptosis within the tumors. Mutations that increase life span by restricting food intake or inhibiting respiration did not affect apoptosis but reduced tumor cell division. Unexpectedly, none of these longevity mutations affected mitosis in normal germlines; this finding suggests that cellular changes that lead to longevity preferentially antagonize tumor cell growth.
Two distinct estrogen‐regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B.

The human progesterone receptor (hPR) cDNA, synthesized from T47D breast cancer cells, and the hPR gene 5′‐flanking region were cloned and sequenced. Comparison of the cDNA‐deduced amino acid sequence with other PR homologues demonstrated the modular structure characteristic of nuclear receptors. As in the case of the chicken homologue, there are two hPR forms, A and B, which originate from translational initiation at AUG2 (codon 165) and AUG1, respectively. Northern blot analysis of T47D mRNA using various cDNA derived probes identified two classes of hPR mRNAs, one of which could code for hPR form B, while the other one lacked the 5′ region upstream of AUG1. S1 nuclease mapping and primer extension analyses confirmed that the second class of hPR transcripts are initiated between +737 and +842 and thus encode hPR form A, but not form B. By using the hPR gene 5′‐flanking sequences as promoter region in chimeric genes, we show that a functional promoter (located between ‐711 and +31) directs initiation of hPR mRNAs from the authentic start sites located at +1 and +15. Most importantly, initiation of transcription from chimeric genes demonstrated the existence of a second promoter located between +464 and +1105. Transient co‐transfection experiments with vectors expressing the human estrogen receptor showed that both promoters were estrogen inducible, although no classical estrogen responsive element was detected in the corresponding sequences. When transiently expressed, the two hPR forms similarly activated transcription from reporter genes containing a single palindromic progestin responsive element (PRE), while form B was more efficient at activating the PRE of the mouse mammary tumor virus long terminal repeat. Transcription from the ovalbumin promoter, however, was induced by hPR form A, but not by form B.
Multiple-Touch-Sensitive Keyboard

In this presentation, we discuss and demonstrate a multiple touch sensitive (MTS) keyboard developed by Robert Moog for John Eaton. Each key of the keyboard is equipped with sensors that detect the three-dimensional position of the performer's finger. The presentation includes some of Eaton's performances for certain earlier prototypes as well as this keyboard.
Gilbert syndrome redefined: A complex genetic haplotype influences the regulation of glucuronidation

Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for UGT1A (UGT1A1*28, UGT1A3‐66 T>C, UGT1A6*3a, UGT1A7*3) and transporter single nucleotide polymorphisms (SNPs) (SCLO1B1 p.V174A, SCLO1B1 p.N130D, ABCC2 p.I1324I, ABCC2‐24 UTR) using TaqMan‐5′‐nuclease‐assays. A humanized transgenic UGT1A‐SNP and corresponding wildtype mouse model were established carrying the GS‐associated UGT1A variant haplotype. UGT1A transcript and protein expression, and transcriptional activation were studied in vivo. Homozygous UGT1A1*28 GS individuals were simultaneously homozygous for UGT1A3‐66 T>C (91%), UGT1A6*2a (77%), and UGT1A7*3 (77%). Seventy‐six percent of GS and only 9% of HBD were homozygous for the variant haplotype spanning four UGT1A genes. SCLO1B1 and ABCC2 SNPs showed no differences. In transgenic humanized UGT1A SNP and wildtype mice this UGT1A haplotype led to lower UGT1A messenger RNA (mRNA) expression and UGT1A protein synthesis. UGT1A transcriptional activation by dioxin, phenobarbital, and endotoxin was significantly reduced in SNP mice. Conclusion: Our data redefine the genetic basis behind GS. In vivo data studying the genotype present in 76% of GS individuals suggest that transcription and transcriptional activation of glucuronidation genes responsible for conjugation and detoxification is directly affected, leading to lower responsiveness. This study suggests that GS should be considered a potential risk factor for drug toxicity. (HEPATOLOGY 2012;55:1912–1921)
The Roles of Telehealth Tools in Supporting Family Caregivers: Current Evidence, Opportunities, and Limitations.

T demands for caregiving are increasing as a result of a constant rise in the aging population and patients with chronic conditions. There are more than 40 million U.S. adults serving as informal caregivers for a family member or friend (National Alliance for Caregiving & AARP, 2015). Main caregiving tasks include assisting the care recipient in activities of daily living (ADLs), performing medical/ nursing care tasks, monitoring the patient’s health and symptoms, communicating with health care professionals, and serving as the patient’s advocate when navigating the health care system. Most family caregivers do not receive any formal caregiving training but are still asked to provide such a wide array of complex tasks for their care recipient. Family caregivers need more information and training on caregiving as well as supportive tools to facilitate stress management and enhance their coping skills. In addition, family caregivers need social support and practical assistance. Telehealth tools, broadly defined as technology-based tools that bridge geographic distance, can be a promising method to deliver interventions designed for family caregivers and enhance access to resources and support. Telehealth technologies are especially important for caregivers living in rural areas or providing remote caregiving. Chi and Demiris (2015) conducted a systematic review of 65 studies that used telehealth interventions to support family caregivers. Telehealth tools that were used included videos (i.e., videoconferencing or videophone solutions), web-based interactive platforms, telephone-based technology (i.e., phone call or text message), and remote monitoring (i.e., electronic data collection and transmission). The types of interventions delivered via telehealth tools were education, consultation (including providing decision support aid), psychosocial/ cognitive-behavioral therapy (including problem-solving training), social support, data collection and monitoring, and clinical care delivery. Below are examples of each type of telehealth tool.
Predicting Honeybee Colony Failure: Using the BEEHAVE Model to Simulate Colony Responses to Pesticides

To simulate effects of pesticides on different honeybee (Apis mellifera L.) life stages, we used the BEEHAVE model to explore how increased mortalities of larvae, in-hive workers, and foragers, as well as reduced egg-laying rate, could impact colony dynamics over multiple years. Stresses were applied for 30 days, both as multiples of the modeled control mortality and as set percentage daily mortalities to assess the sensitivity of the modeled colony both to small fluctuations in mortality and periods of low to very high daily mortality. These stresses simulate stylized exposure of the different life stages to nectar and pollen contaminated with pesticide for 30 days. Increasing adult bee mortality had a much greater impact on colony survival than mortality of bee larvae or reduction in egg laying rate. Importantly, the seasonal timing of the imposed mortality affected the magnitude of the impact at colony level. In line with the LD50, we propose a new index of “lethal imposed stress”: the LIS50 which indicates the level of stress on individuals that results in 50% colony mortality. This (or any LISx) is a comparative index for exploring the effects of different stressors at colony level in model simulations. While colony failure is not an acceptable protection goal, this index could be used to inform the setting of future regulatory protection goals.
Degradation of human immunoglobulins by proteases from Streptococcus pneumoniae obtained from various human sources

The ability of Streptococcus pneumoniae to degrade human secretory immunoglobulin A (S-IgA), IgG, and IgM was tested in 102 strains by use of the thin-layer enzyme assay cultivation technique. The strains were isolated from patients with acute phases of otitis media, meningitis, and pneumonia as well as from symptomless carriers. An ability to degrade S-IgA, IgG, and IgM was revealed in 50, 84, and 96 strains, respectively. An IgG- and IgM-degrading ability of S. pneumoniae has not previously been reported. A concurrent degradation of the three immunoglobulins was revealed in 38 strains; degradation of two of them was revealed in 54 strains, and degradation of only one of them was revealed in 9 strains. One strain failed to degrade any of the immunoglobulins. Correlations were not found between the ability of the S. pneumoniae strains to degrade S-IgA, IgG, or IgM and the serotype affiliation or between the ability to degrade IgG or IgM and the origin of strains. However, the ability to degrade S-IgA was evident more often in strains isolated from symptomless carriers and from bronchial secretions of patients with acute pneumonia than it was in strains from patients with acute meningitis or acute otitis media or from the blood of patients with acute pneumonia. These latter findings may indicate a biological significance of S-IgA-degrading ability in bacterial colonization of mucosal surfaces.
An unconditionally stable 3-D ADI-MRTD method free of the CFL stability condition

In this paper, an alternating direction implicit (ADI) technique is applied to the recently developed multiresolution time-domain (MRTD) method, resulting in an unconditionally stable ADI-MRTD scheme free of the Courant-Friedich-Lecy (CFL) stability condition. The unconditional stability is theoretically proved, and preliminary numerical results are presented to validate the scheme. Because the scheme is now free of the stability condition, its time step is determined only by modeling accuracy. The price for having the unconditional stability is, however, that the required computation memory becomes almost twice of that for the original MRTD.
Flexible and Stretchable Physical Sensor Integrated Platforms for Wearable Human‐Activity Monitoringand Personal Healthcare

Flexible and stretchable physical sensors that can measure and quantify electrical signals generated by human activities are attracting a great deal of attention as they have unique characteristics, such as ultrathinness, low modulus, light weight, high flexibility, and stretchability. These flexible and stretchable physical sensors conformally attached on the surface of organs or skin can provide a new opportunity for human‐activity monitoring and personal healthcare. Consequently, in recent years there has been considerable research effort devoted to the development of flexible and stretchable physical sensors to fulfill the requirements of future technology, and much progress has been achieved. Here, the most recent developments of flexible and stretchable physical sensors are described, including temperature, pressure, and strain sensors, and flexible and stretchable sensor‐integrated platforms. The latest successful examples of flexible and stretchable physical sensors for the detection of temperature, pressure, and strain, as well as their novel structures, technological innovations, and challenges, are reviewed first. In the next section, recent progress regarding sensor‐integrated wearable platforms is overviewed in detail. Some of the latest achievements regarding self‐powered sensor‐integrated wearable platform technologies are also reviewed. Further research direction and challenges are also proposed to develop a fully sensor‐integrated wearable platform for monitoring human activity and personal healthcare in the near future.
Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene

Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of β-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where β-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of β-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells.
Prospective Study of Nut Consumption and Incidence of Metabolic Syndrome: Tehran Lipid and Glucose Study

This study aimed to assess the association of various types of nut per se, and total nut consumption with the incidence of metabolic syndrome (MetS). A 6.2 ± 0.7-year population-based prospective study was conducted among 1265 adults, aged 19–74 years, participants of the Tehran Lipid and Glucose Study. A 168-item semi-quantitative food frequency questionnaire was used to collect information on nut consumption. MetS was defined according to the Joint Interim Statement guidelines and 276 new cases of MetS were identified. Median ± interquartile range of nut consumption was 2.08 (0.88–5.68) servings/week. After adjusting for family history of diabetes, age, gender, smoking, physical activity, fasting serum glucose at baseline, serum high density lipoprotein cholesterol (HDL-C) at baseline, energy intake, fiber, macronutrients, cholesterol intake, fruit, vegetables, dairy products and body mass index (BMI), a statistically significant decrease was observed in MetS in the third (≥5 servings/week) tertile of nuts (odds ratio: 0.68, 95% CI: 0.44–0.91, p trend: 0.03) compared with the lowest (≤1 serving/week). Walnut consumption showed a significant, inverse association with MetS risk; associations for other nut varieties were not significant. For each additional serving/week of walnuts consumed, incidence of MetS decreased by 3% (ORs: 0.97 CI: 0.93–0.99), after adjusting for confounding factors. Total nut consumption, especially walnuts, reduces the risk of MetS.
Brief Exercise Counseling and High-Intensity Interval Training on Physical Activity Adherence and Cardiometabolic Health in Individuals at Risk of Type 2 Diabetes: Protocol for a Randomized Controlled Trial

Background Worldwide incidence of type 2 diabetes (T2D) is rapidly increasing. Given the numerous negative health consequences associated with T2D, prevention of this disease has become a priority. Lifestyle changes, including regular exercise, can reduce the onset of T2D in those at elevated risk. However, long-term adherence to exercise is often poor in this population. Existing lifestyle interventions targeting exercise are labor intensive and costly for staff and participants. Evidence-informed counseling delivered in a manner that reduces dependence on staff and facilitates self-regulatory skills could alleviate time and financial barriers while promoting independent exercise. Objective This protocol outlines the design, recruitment, and proposed analysis of a brief, 2-week evidence-informed exercise counseling intervention combined with either high-intensity interval training (HIIT) or traditional moderate-intensity continuous training (MICT). Methods Small Steps for Big Changes is a 2-arm randomized controlled trial that will examine the effectiveness of combining brief exercise counseling with HIIT or MICT on adherence to moderate and vigorous exercise over 1 year. Cardiorespiratory fitness will be assessed at baseline, post intervention (2 weeks), and at 6- and 12-month follow-up. Physical activity behavior will be examined at baseline, post intervention, and 3-, 6-, 9-, and 12-month follow-up. The impact of the intervention on psychosocial outcomes pertinent to exercise adherence will be examined. Results Data collection was complete in March 2017. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2019. Conclusions The results of this brief intervention have the potential to inform future public health efforts designed to increase exercise in individuals at risk of T2D. Trial Registration ClinicalTrials.gov NCT02164474; https://clinicaltrials.gov/ct2/show/NCT02164474 (Archived by WebCite at http://www.webcitation.org/74Hx1ipj6) International Registered Report Identifier (IRRID) DERR1-10.2196/11226
Development and Assessment of an E-Learning Course on Breast Imaging for Radiographers: A Stratified Randomized Controlled Trial

Background Mammography is considered the best imaging technique for breast cancer screening, and the radiographer plays an important role in its performance. Therefore, continuing education is critical to improving the performance of these professionals and thus providing better health care services. Objective Our goal was to develop an e-learning course on breast imaging for radiographers, assessing its efficacy, effectiveness, and user satisfaction. Methods A stratified randomized controlled trial was performed with radiographers and radiology students who already had mammography training, using pre- and post-knowledge tests, and satisfaction questionnaires. The primary outcome was the improvement in test results (percentage of correct answers), using intention-to-treat and per-protocol analysis. Results A total of 54 participants were assigned to the intervention (20 students plus 34 radiographers) with 53 controls (19+34). The intervention was completed by 40 participants (11+29), with 4 (2+2) discontinued interventions, and 10 (7+3) lost to follow-up. Differences in the primary outcome were found between intervention and control: 21 versus 4 percentage points (pp), P<. 001. Stratified analysis showed effect in radiographers (23 pp vs 4 pp; P=.004) but was unclear in students (18 pp vs 5 pp; P=.098). Nonetheless, differences in students’ posttest results were found (88% vs 63%; P=.003), which were absent in pretest (63% vs 63%; P=.106). The per-protocol analysis showed a higher effect (26 pp vs 2 pp; P<.001), both in students (25 pp vs 3 pp; P=.004) and radiographers (27 pp vs 2 pp; P<.001). Overall, 85% were satisfied with the course, and 88% considered it successful. Conclusions This e-learning course is effective, especially for radiographers, which highlights the need for continuing education.
The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity.

OBJECTIVE The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. METHOD The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly. RESULTS The expert panel ratings are presented for the initially selected 36 tests. For the beta battery tests, data on test-retest reliability, practice effects, relationships to functional status, practicality, and tolerability are presented. Based on these data, 10 tests were selected to represent seven cognitive domains in the MATRICS Consensus Cognitive Battery. CONCLUSIONS The structured consensus method was a feasible and fair mechanism for choosing candidate tests, and direct comparison of beta battery tests in a common sample allowed selection of a final consensus battery. The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia. It may also aid evaluation of cognitive remediation strategies.
Transmembrane Topology and Oligomeric Structure of the High-affinity Choline Transporter*

Background: The structure-function relationship of the high-affinity choline transporter CHT1 is largely unknown. Results: Cysteine-scanning analysis and cross-linking/co-immunoprecipitation were used to determine the structural properties of CHT1. Conclusion: CHT1 is a 13-transmembrane domain protein and forms a homo-oligomer on cell surface. Significance: This might be the first molecular evidence of homo-oligomerization in the Na+/glucose cotransporter family (SLC5). The high-affinity choline transporter CHT1 mediates choline uptake essential for acetylcholine synthesis in cholinergic nerve terminals. CHT1 belongs to the Na+/glucose cotransporter family (SLC5), which is postulated to have a common 13-transmembrane domain core; however, no direct experimental evidence for CHT1 transmembrane topology has yet been reported. We examined the transmembrane topology of human CHT1 using cysteine-scanning analysis. Single cysteine residues were introduced into the putative extra- and intracellular loops and probed for external accessibility for labeling with a membrane-impermeable, sulfhydryl-specific biotinylating reagent in intact cells expressing these mutants. The results provide experimental evidence for a topological model of a 13-transmembrane domain protein with an extracellular amino terminus and an intracellular carboxyl terminus. We also constructed a three-dimensional homology model of CHT1 based on the crystal structure of the bacterial Na+/galactose cotransporter, which supports our conclusion of CHT1 transmembrane topology. Furthermore, we examined whether CHT1 exists as a monomer or oligomer. Chemical cross-linking induces the formation of a higher molecular weight form of CHT1 on the cell surface in HEK293 cells. Two different epitope-tagged CHT1 proteins expressed in the same cells can be co-immunoprecipitated. Moreover, co-expression of an inactive mutant I89A with the wild type induces a dominant-negative effect on the overall choline uptake activity. These results indicate that CHT1 forms a homo-oligomer on the cell surface in cultured cells.