cssi/SciSciGPT-SciSciNet huggingface dataset:
Environmental and Genetic Susceptibility to MLL-Defined Infant Leukemia

The study of rare cancers, including retinoblastoma, angiosarcoma, and vaginal clear cell carcinoma, has contributed greatly to our understanding of cancer mechanisms. Infants with leukemia may represent another important rare group. The majority of infants with leukemia have MLL gene rearrangements in their leukemia cells, and there is unequivocal laboratory evidence that these arise in utero. There is increasing evidence that environmental and genetic factors may contribute to the risk of MLL-defined infant leukemias. Because the infant exposure experience is only a small window in comparison to that of an individual who develops a malignancy in middle or late age, the pivotal factors responsible for this genetic anomaly may be easier to identify. With the largest case-control study of infant leukemia ever conducted underway in the Children's Oncology Group (COG AE24), there is a unique opportunity to integrate epidemiological data with laboratory data on MLL status and genotype.
Dual use of condoms and contraceptives in the USA.

Background: Use of condoms in conjunction with other contraceptive methods has multiple benefits: prevention of unintended pregnancy, protection against sexually transmissible infections (STI), and sequentially, defence against the threat of infertility. However, few reviews compare dual method use prevalence or trends or systematically review the facilitators and barriers of dual method use across multiple studies. Methods: The authors review the literature on trends and covariates of dual method use in the USA among both nationally representative and smaller samples. Results: Although dual method use prevalence estimates vary widely across study populations, nationally representative estimates are consistently lower than Western European countries, who in turn report lower rates of unintended pregnancies and STI. The majority of published work on dual method use focuses on adolescents. Prior studies have associated dual method use with a range of individual-level factors: socio-demographic variables, such as younger age; STI risk behaviours and risk perception; relationship variables, such as number of partners, relationship length, and partner support of condoms; and educational factors, such as prior exposure to HIV prevention messages. Conclusions: Although dual method use appears to be on the rise, especially among adolescents and young adults, US rates are comparatively low and leave much room for improvement. This review identifies several populations most in need of intervention. However, we encourage public health practitioners to evolve beyond individual-level studies and interventions to focus on the relational, socio-cultural, and structural influences on dual method use. Dual use promotion programs and policies should also equally target men and women, adolescents and adults.
Molecular mechanisms in photodynamic action.

— Photodynamic action can be considered at the molecular level as a dye-sensitized photoautoxidation of the biological substrate. Recent work has shown that interactions of a sensitizing dye, such as occur in aggregation or binding, can lead to significant changes in its photochemical reactivity. The possible role of such effects in the primary photodynamic mechanism is reviewed.
Experimental S F 6 − / S F 6 and Cl − / CF Cl 3 Electron-Attachment Cross Sections in the Energy Range 0-200 meV

Experimental cross sections for the electron-attachment processes for S${\mathrm{F}}_{6}^{\ensuremath{-}}$/S${\mathrm{F}}_{6}$ and ${\mathrm{Cl}}^{\ensuremath{-}}$/CF${\mathrm{Cl}}_{3}$ are reported in the energy range 0-200 meV by normalizing each attachment line shape to measurement of a thermal rate coefficient. When the same ion states are detected, good agreement is found between present values, for which a monoenergetic electron source is used, and swarm-unfolded results. The present data constitute a new limit for cross sections reported at high resolution at the lowest electron energy.
Higher Orders of Chromatin Structure

We describe recent studies of the 30 nm fiber, in which we have used electric dichroism to determine the orientation of chromatosomes within the chromatin fiber. We show that data obtained with chromatin from a variety of sources, and with varying spacer length, suggest a similar packing of the chromatosomes in all 30 nm fibers. We also discuss factors that might affect the stability of the fiber, particularly in such a way as to render the DNA it contains more accessible for transcription.
Interactive Voice Recognition Communication in Electoral Politics Exploratory Metadata Analysis

This research tested the conventional wisdom that interactive voice recognition (IVR; also known as robocalls or auto calls) are not listened to by receivers. The study found that three out of four people (75%) listen to over 19 s of a message, which equates to over 40 words. The vast majority of people, 97%, listen to at least 6 s. This innovative, unobtrusive field approach for measuring actual listening time eliminates self-report bias. The unique data set, provided by a third-party vendor, consisted of 156 call projects with a total of 389,588 live answered phone calls from the last week of the 2012 election.
Gamma Irradiation of Pupae of the Tobacco Budworm

Pupae of the tobacco budworm, Heliothis virescen (F.), were irradiated with Cobalt-60 gamma rays about 2 days before adult emergence. Male moths were 99% sterile after a dose of 35 kilorads. Female moths produced very few eggs when the dose was greater than 35 krad, though there was some egg hatch at this dose level. The emergence and lifespan of both sexes were reduced by sterilizing doses. The initiation and length of the oviposition periods for females mated with either treated males or untreated males were similar. However, females crossed with treated males produced significantly fewer eggs. Virgin females laid eggs, but their oviposition began later and was shorter than that of females crossed with males. The average lifetime production of eggs for single pairs of control moths was about 800 eggs, though some females did produce more than 1600. When the sterility data from irradiated males were plotted, the resulting dose-response curve appeared to be sigmoidal. Cytological observations on spermatogenesis indicated that sperm were present in the testes of the pupae at the time of irradiation.
BP Neural Network Tuning PID Algorithm for Precision Control of Functional Electrical Stimulation

To solve the problem of current intensity precision control for functional electrical stimulation(FES)and guarantee its exact stimulation effect to perform preset action,a back-propagation(BP)artificial neural network model with three layers was proposed to tune the parameters of traditional proportional-integral-derivative(PID)controller.Stimulation current intensity of FES system was accurately and stably modulated through a real-time feedback control based on the trajectory of knee joint angle.The control effect was evaluated by the deviation between real and preset trajectory of knee joint angle and the root mean square(RMS)of deviation in PID whole control process.Experimental results show that,in comparison with traditional Ziegler-Nichols tuning PID algorithm,the proposed method gets a lower deviation error of stimulation current intensity for FES system control,which makes the preset trajectory better matching the real trajectory of knee joint angle with more stable rehabilitation training effect.
Ethics and Health Policy

A career in the ethics of health policy is not necessarily a straight line. Starting from an academic interest in medical ethics, and without any concerns specifically about policy, I have gradually expanded my horizons to include a number of policy questions. I’ll recount here what led me to shift my interests into a policy direction, what immediate lessons I took away from that experience, and finally, what longer-term questions seem to remain.
Immunoreactive tissue kallikrein in human serum.

Abstract Human urinary kallikrein and an antiserum to it raised in the rabbit were used to detect and quantitate immunoreactive tissue kallikrein in human serum. Both 125 I-labeled kallikrein and the unlabeled purified enzyme appear complexed to higher molecular weight entities in serum, but specific binding between radiolabeled enzyme and antiserum was unaffected by the presence of serum or plasma. Parallelism to standard displacement curves was always seen with radioimmunoassay of normal sera as well as with human mixed saliva or pancreatic extracts. Assay sensitivity is 160 pg/ml of serum, or 16 pg per tube. Purified plasma kallikrein or prekallikrein in concentrations up to 10 μg/ml showed no displacement. Acetone-kaolin activation of plasma produced the expected 30-fold increase in Tos-Arg-OMe esterase activity but no change in immunoreactive tissue kallikrein levels. Serum concentrations were 3.8 ± 0.7 (mean ± SE) ng/ml in 21 normal volunteers, and were similar in patients with Fletcher trait or Hageman factor deficiency. Significantly increased serum concentrations were seen with long-term low dietary sodium intake or acute forms of pancreatitis. Although the relation of this immunoreactive material to any active tissue kallikrein within the circulation remains to be determined, our studies provide a new parameter for the assessment of a system repeatedly suggested to have some role in regulation of vascular resistance.
Effects of Plume-Related Thermal Anomaly

The rise of axisymmetric thermal plumes from the core-mantle boundary (CMB) in a compressible fluid can be modeled using equations for inelastic, compressible fluids with infinite Prandtl number convection (Jarvis and McKenzie, 1980).
Songs of the Alder Flycatcher (Empidonax alnorum) and Willow Flycatcher (Empidonax traillii) are Innate

-I studied the song development of five Willow Flycatchers (Empidonax traillii) and four Alder Flycatchers (Empidonax alnorum) taken from nests at 7-10 days of age. Three Willow Flycatchers and four Alder Flycatchers were tutored with songs of the other species, and two Willow Flycatchers served as controls, hearing only conspecific songs. All nine subjects, both females (when administered exogenous testosterone) and males, and both experimentals and controls, produced remarkably normal songs; slight differences between songs of wild and experimental subjects could be attributed to motivational states rather than to the effects of acoustic isolation in the laboratory. I found no microgeographic variation of wild songs, no evidence of learning from a tutor tape, nor any similarity of song characters among kin. The vocal development of these suboscine flycatchers is strikingly different from that of typical oscines, where vocal learning is the rule. Received 17 January 1983, accepted 1
VHDL-AMS behavioral modeling and simulation of a /spl Pi//4 DQPSK transceiver system

This work describes a methodology for top-down design, modeling, and simulation of complete /spl Pi//4 DQPSK system using hardware description language VHDL-AMS. Two system implementations are considered: with and without Viterbi encoder/decoder. VHDL-AMS implementations of various RF blocks (e.g. a realistic channel model) are developed, the system is simulated, and bit error rate is evaluated in the presence of noise. We show that the results of VHDL-AMS simulations for basic /spl Pi//4 DQPSK system in Mentor Graphics ADVance-MS match both Agilent ADS results and theoretical calculations. Adding a simple Viterbi encoder and decoder in VHDL to the basic system results in an approximate 1.4 dB SNR improvement. This work together is targeted towards engineers who work on behavioral modeling and simulation of complete RF systems using hardware description languages.
Decitabine Can Induce Complete Cytogenetic Responses When Used as Initial Therapy in Older AML Patients.

Abstract 4123 Background The incidence of acute myeloid leukemia (AML) increases with advancing age. At present, there are limited treatment options available for older patients because of lack of efficacy and increased toxicity. In a previously reported Phase II AML trial (n = 55), older patients not previously treated for AML experienced an overall response rate of 25% with decitabine (Cashen et al. Blood 2008). Response rate was similar in patients with poor or intermediate cytogenetic risk at baseline. In addition, 5 (15%) of the 34 patients who had cytogenetic abnormalities at baseline achieved a complete cytogenetic response in this trial. As older AML patients are more likely to present with unfavorable cytogenetic profiles, it was of interest to review the patient characteristics and describe the responses of the 5 patients who had a complete cytogenetic response. Methods The patients for this analysis were from a multicenter, Phase II study. In this study, patients over the age of 60 with AML (>20% bone marrow blasts) and no prior therapy for AML were treated with decitabine, 20 mg/m 2 IV for 5 consecutive days of a 28-day cycle until disease progression or unacceptable adverse event. Cytogenetic profile was assessed at screening and after every cycle, beginning with cycle 2. Results The 5 patients (2 males, 3 females; 5 white; 2 M1, 1 each for M2, M6, and M7) with a complete cytogenetic response had baseline characteristics that are associated with high risk. Three were >70 yrs of age, and all 5 had AML secondary to prior therapy (n=2) or MDS (n=3). Four patients had poor-risk cytogenetics: 2 pts with -7, -5q, and ≥ 3 abnormalities and 2 pts with deletions of chromosome 5 and ≥ 3 abnormalities. One patient had intermediate-risk cytogenetics. The median baseline bone marrow myeloblast count was 33% (range 21 to 60). These patients were treated with a median 10 cycles (range 6 to 19) of decitabine. The median time to a complete cytogenetic response was 5 cycles (range 2.3 to 6). The median time to relapse from a complete cytogenetic response was 8.1 cycles (range 3.4 to 19.8). The overall median survival was 21.6 months (95% CI: 9.5, 24.7), which compares favorably to the median overall survival of the entire study cohort (21.6 months vs. 7.7 months, Cashen et al. Blood 2008). Conclusions Treatment with decitabine can induce complete and durable cytogenetic responses, even in older patients with high risk disease characteristics and poor risk cytogenetics. Patients who achieve a cytogenetic response may have a survival benefit. A presently ongoing Phase III survival trial with decitabine will help further characterize the effect of decitabine on cytogenetic responses in older AML patients. Disclosures: Cashen: Eisai, Inc.: Consultancy.
Application of Panel-Based Tests for Inherited Risk of Cancer.

Next-generation or massively parallel sequencing has transformed the landscape of genetic testing for cancer susceptibility. Panel-based genetic tests evaluate multiple genes simultaneously and rapidly. Because these tests are frequently offered in clinical settings, understanding their clinical validity and utility is critical. When evaluating the inherited risk of breast and ovarian cancers, panel-based tests provide incremental benefit compared with BRCA1/2 genetic testing. For inherited risk of other cancers, such as colon cancer and pheochromocytoma-paraganglioma, the clinical utility and yield of panel-based testing are higher; in fact, simultaneous evaluation of multiple genes has been the historical standard for these diseases. Evaluating inherited risk with panel-based testing has recently entered clinical practice for prostate and pancreatic cancers, with potential therapeutic implications. The resulting variants of uncertain significance and mutations with unclear actionability pose challenges ...
Selective Synthesis of Substituted 3-Aryl-2-phenyl-1,3-thiazolidin-4-one Sulfoxides and Sulfones by S-Oxidation with Oxone

S-oxidation of 3-aryl-2-phenyl-1,3-thiazolidin-4-ones with Oxone® was investigated. For all compounds evaluated, selective oxidation to the sulfoxide was realized using 3 equivalents of Oxone® at room temperature. Alternatively, the sulfone was prepared selectively in most of the compounds evaluated at high temperature by increasing the equivalents of Oxone® used; the extent of this selectivity was affected by the substituent and its position on the N3 aromatic ring. The ratio of the sulfoxide and sulfone products was quantified by isolating the products by liquid chromatography.
Single Anastomosis Duodeno-Ileal Switch (SADIS): A Systematic Review of Efficacy and Safety

Owing to the possibility of weight regain after the long-term follow-up of gastric bypass patients and because of the high morbidity of biliopancreatic diversion with duodenal switch, single-anastomosis duodeno-ileal switch (SADIS) has emerged as a rescue procedure in bariatric surgery. The purpose of this review is to summarize the literature data on SADIS. University Hospital, NY. A comprehensive literature review was performed through October 2016 to identify English studies on SADIS performed in human subjects. Outcomes of interest were technical considerations, postoperative complications, weight loss outcome, comorbidity resolution rate, and nutritional deficiency after SADIS. A total of 12 studies including 581 SADIS patients (217 males and 364 females) were included. SADIS was a primary procedure in 508 patients (87.4%) and a conversion procedure in 73 patients (12.6%). The length of common limb was 300 cm in 54.2%, 250 cm in 23%, and 200 cm in 13.4% of patients. Anastomosis technique was a linear stapler in 26.7% and a hand sewn suture technique in 73.3% of patients. Diarrhea was the most common complication (1.2%). The average %EWL was 30% at 3 months, 55% at 6 months, 70% at 1 year, and 85% at 2 years. Co-morbidity resolution rate was 74.1% for type 2 diabetes mellitus, 96.3% for hypertension, 68.3% for dyslipidemia, 63.3% for obstructive sleep apnea, and 87.5% for GERD. Overall, vitamin A, selenium, and iron deficiency were the most common nutritional deficiencies with the possibility of the protein malnutrition in up to 34% of the patients when measured. As a modified bariatric procedure, SADIS has promising outcomes for weight loss and comorbidity resolution in morbidly obese patients. When measured, there was a high prevalence of macro-nutrient deficiencies following SADIS. There is a high technical variability, and long-term data are required before any meaningful conclusion can be made.
Longitudinal Associations between Gender and Ethnic-Racial Identity Felt Pressure from Family and Peers and Self-Esteem among African American and Latino/a Youth

Gender identity felt pressure is negatively associated with adjustment indices, including self-esteem, among children and early adolescents, and both gender and ethnic-racial identity felt pressure are negatively associated with self-esteem among young adults. This study explored the longitudinal associations between gender identity and ethnic-racial identity felt pressure from family and peers to behave in either gender or race/ethnic-accordant ways, and self-esteem among a sample of 750 (49.2% female) African American (n = 194) and Latino/a youth (n = 556) (M = 12.10 years, SD = .97 years). For African Americans, the results revealed significant negative longitudinal associations between (a) ethnic-racial identity felt pressure from family at Time 1 and self-esteem at Time 2 and (b) ethnic-racial identity felt pressure from peers at Time 1 and self-esteem at Time 2, controlling for self-esteem at Time 1. These associations were not found among Latinos/as, nor were associations found between gender identity felt pressure from peers or family and self-esteem. The findings are discussed by drawing on the gender identity and ethnic-racial identity literatures.
Optimized induction of beta common receptor enhances the neuroprotective function of erythropoietin in spinal cord ischemic injury.

Abstract Background Paraplegia remains the most feared complication of complex thoracoabdominal aortic intervention. Although erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, it does not work until expression of the beta common receptor subunit of the EPO receptor (βcR) is induced by ischemia. We hypothesized that the βcR can be induced by diazoxide (DZ), amplifying the neuroprotective effects of EPO in spinal cord ischemia-reperfusion injury. Methods For the DZ time trial, adult male C57/BL6 mice received DZ (20 mg/kg) by oral gavage. Spinal cords were harvested after 0, 12, 24, 36, and 48 hours of administration. To evaluate optimal dosing, DZ was administered at 0, 5, 10, 20, and 40 mg/kg. The expression of βcR was assessed by Western blot analysis. Five groups were studied: PBS (pretreatment)+PBS (immediately before), PBS+EPO, DZ+PBS, DZ+EPO, and sham (without cross-clamping). Spinal cord ischemia was induced by 4 minutes of thoracic aortic cross-clamping. Functional scoring (Basso Mouse Score) was done at 12-hour intervals for 48 hours, and spinal cords were harvested for histological analysis. Results Western blot analysis demonstrated that optimal βcR up-regulation occurred at 36 hours after DZ administration, and the optimal DZ dosage for βcR induction was 20 mg/kg. Motor function at 48 hours after treatment was significantly better preserved in the DZ+EPO group compared with all other groups, and was significantly better preserved in the DZ only and EPO only groups compared with control (PBS+PBS). Conclusions Pharmacologic up-regulation of βcR with DZ can increase the efficacy of EPO in preventing spinal cord ischemia and reperfusion injury. Improved understanding of this synergetic mechanism may serve to further prevent ischemic complications for high-risk aortic intervention.
Motivated attention to fear-related stimuli: Evidence for the enhanced processing of fear in the late positive potential

Differences in the processing of emotions like fear and sadness have important implications for our understanding of many psychological phenomena (e.g., attentional biases, psychopathology). The late positive potential (LPP) is an established event-related potential that reflects motivated attention to emotional stimuli at the neural level with excellent temporal resolution, but has been infrequently used to study differences across emotions. Drawing on functional theories of emotion suggesting that the quick processing of fear-inducing stimuli increases chances of survival, we hypothesized that fear-inducing pictures would produce larger LPP amplitudes compared to other emotions (happy and sad) in the early time windows of the LPP (e.g., 400–700, 700–1000 ms). The results supported our hypothesis, offering new, albeit preliminary, evidence of the differential processing of threat-related stimuli on the LPP.
Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need.

Imagine that you have just finished Thanksgiving dinner. You are completely full, having eaten large portions of turkey, green beans and mashed potatoes. Yet, despite feeling full, you still find yourself tempted by a slice of pie for dessert, maybe even with ice cream on top. Why is it that in such a state of fullness, you desire a slice of pie but not, say, another helping of green beans? The answer may lie in the way the brain responds to food when we do not need any more calories. At such times, your brain drives you to continue eating only those foods that are tasty and calorie-dense. This preference for fatty and sweet foods may have been helpful in the past when we could not be certain where our next meal would come from. But in modern times, the widespread availability of food makes this preference potentially harmful. For example, the drive to consume fatty and sweet foods even when not hungry may now be contributing to soaring levels of obesity and type 2 diabetes. What exactly is happening inside the brain to produce this behavior? Previous work has implicated a structure called the nucleus accumbens. When scientists activated proteins called mu opioid receptors within the nucleus accumbens, animals ate more of the foods that they find tasty. However, they were not as interested in eating more of the foods that they are more ambivalent towards. Caref and Nicola now show that preventing opioid binding makes rats unwilling to respond to a cue to obtain cream, an appetizing, high-fat reward. It also abolishes the brain activity that drives the rats to respond the cue. Crucially, however, this effect only occurs in rats that are not hungry. It therefore appears that opioid binding in the nucleus accumbens drives animals to approach and eat high-fat foods, but only when they do not need the calories. That is, it increases fat consumption in animals that are not actually hungry. A drug that selectively blocks mu opioid receptors in the nucleus accumbens may reduce this behavior. Such a drug could potentially help to prevent obesity and the health problems associated with it.
Blood based biomarkers beyond genomics for lung cancer screening

While there is considerable interest at the present time in the development of so-called liquid biopsy approaches for cancer detection based notably on circulating tumor DNA, there are other types of potential biomarkers that show promise for lung cancer screening and early detection. Here we review approaches and some of the promising markers based on proteomics, metabolomics and the immune response to tumor antigens in the form of autoantibodies.
Civil war termination and foreign direct investment, 1989–2012:

Data on global foreign direct investment (FDI) inflows shows that civil war significantly deters investment, while post-civil war settings attract investment. Civil wars, however, can end in differ...
Setting the pace for VISION 2020 in Ghana: the case of Bawku Eye Care Programme.

Ghana is a west African country bordered on the south by the Atlantic Ocean, and the north, east, and west by the Republics of Burkina Faso, Togo, and Ivory Coast respectively. It has a population of 20,771,382. Prevalence of blindness is estimated at one per cent. It currently has 52 ophthalmologists and 216 ophthalmic nurses (National Eye Care Secretariat), with nearly half of the ophthalmologists (19) located in the national capital and its environs. The health sector attracted 7.9 per cent of government budget in 2002 and 12.3 per cent in the 2006 budget. Currently there is a comprehensive national health insurance policy being implemented that covers most of the common eye operations done in the country.
20 Years from NCX Purification and Cloning: Milestones

The Na+/Ca2+ exchanger protein was first isolated from cardiac sarcolemma in 1988 and cloned in 1990. This allowed study of Na+/Ca2+ exchange at the molecular level to begin. I will review the story leading to the cloning of NCX and the research that resulted from this event. This will include structure-function studies such as determination of the numbers of transmembrane segments and topological arrangement. Information on ion transport sites has been gathered from site-directed mutagenesis. The regions involved in Ca2+ regulation have been identified, analyzed, and crystallized.
Leucine Supplementation Partially Protects Leg Lean Mass in Older Adults During Seven Days of Bed Rest (OR18-02-19)

Older adults are at increased risk of being hospitalized or bedridden and experiencing a host of negative health outcomes including loss of lean body mass. We hypothesized that supplementing daily meals with a small quantity (3–4 g/meal) of leucine will partially preserve lean leg mass and function during bed rest. Men and women (67.8 ± 1.1 y) were randomized to receive isoenergentic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control, (CON, 0.06 g/kg/meal; n = 10). Subjects were admitted to the Clinical Research Center for 7 days of bed rest followed by 7 days of rehabilitation. Muscle fiber type and cross-sectional area (CSA) as well as single fiber characteristics were assessed from biopsies of the vastus lateralis obtained prior to (Pre-BR) and after bed rest (Post-BR) and after rehabilitation (Post-RE). Body composition measured using iDEXA was also determined at the same time points. Leucine-supplementation partially protected leg lean mass during bed rest (−1035 vs. −423 ± 143 g; P = 0.008). Leg lean mass did not differ between the groups Post-RE (P = 0.16). There was no significant effect of time (P = 0.16) or treatment (P = 0.92) on muscle fiber CSA; however, CON subjects, but not LEU subjects, exhibited an increased number of smaller fibers ( 6000 um) Post-BR. Additionally, CON subjects tended to have a greater decrement in fiber width (P = 0.085) that did not return to baseline following rehabilitation. Supplementing older adults with moderate amounts of leucine has the potential to partially negate some of the deleterious effects on muscle health during short bouts of inactivity. National Institutes of Health, The Claude D. Pepper Older Americans Independence Center, Sealy Center on Aging and Institute for Translational Sciences-Clinical Research Center.
Parent-Implemented Language Intervention for Teaching Enhanced Milieu Teaching Strategies to Parents of Low-Socioeconomic Status:

In this study, the authors examined the effects of training four parents from low-socioeconomic environments to use Enhanced Milieu Teaching (EMT) with their young children with language delay. Par...
Biomimetic nanovesicles made from iPS cell-derived mesenchymal stem cells for targeted therapy of triple-negative breast cancer

Nanoparticles made from membrane of mesenchymal stem cells (MSCs) showed active targeting capacities to prostate and lung cancers, but further studies are hindered by limited expandability and donor variations of tissue-derived MSCs. We have derived MSCs with an unlimited supply and uniform homing capacity to triple-negative breast cancer (TNBC) from human induced pluripotent stem cells (iPSCs). By breaking down intact iPSC-MSCs, we efficiently developed nanovesicles that selectively accumulated in primary and metastatic TNBC after systemic infusion in mouse models. When loaded with a chemotherapeutic drug doxorubicin, iPSC-MSC nanovesicles showed superior cytotoxic effects on doxorubicin-resistant TNBC cells, and significantly decreased the incidence and burden of metastases in mouse models of spontaneous and experimental metastatic TNBC compared with free or liposomal doxorubicin. These nanovesicles showed no detectable immunogenicity or toxicity, and are stable after storage. Our data indicate that iPSC-MSC nanovesicles are promising to improve TNBC treatment as a standardized targeting platform.
Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling

Aims Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes. Methods and results Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFβ signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFβ signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFβ pathway genes. Conclusion Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFβ pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.
SEUSS: skip redundant paths to make serverless fast

This paper presents a system-level method for achieving the rapid deployment and high-density caching of serverless functions in a FaaS environment. For reduced start times, functions are deployed from unikernel snapshots, bypassing expensive initialization steps. To reduce the memory footprint of snapshots we apply page-level sharing across the entire software stack that is required to run a function. We demonstrate the effects of our techniques by replacing Linux on the compute node of a FaaS platform architecture. With our prototype OS, the deployment time of a function drops from 100s of milliseconds to under 10 ms. Platform throughput improves by 51x on workload composed entirely of new functions. We are able to cache over 50,000 function instances in memory as opposed to 3,000 using standard OS techniques. In combination, these improvements give the FaaS platform a new ability to handle large-scale bursts of requests.
An Online Doctorate for Researching Professionals

An Online Doctorate for Researching Professionals was written with the view of using new perspective in expanding the horizon of PhD students in higher education. The authors considered the development of online programs to meet the needs of the working professionals. This became necessary because the traditional PhD programs in education was not enough to meet the desires of the working professionals in combining the furthering of their education and carrying out applied research skills with continuing full-time employment. The authors presented their model that focused on an online professional doctorate program which combined theory research and practice.
Structuring Disruption within University-Based Teacher Education Programs1: Possibilities and Challenges of Race-Based Caucuses:

BackgroundTeacher education candidates are in different places in terms of developing their identities and relationships to equity and social justice. Various approaches have been taken within univ...
The case for Culturally and Linguistically Relevant Pedagogy: Bilingual Reading to learn for Spanish-Speaking immigrant mothers

Abstract Michael Halliday’s threefold language learning principle, “learning language, learning through language, and learning about language” (Halliday, 1993), is an important yet underused insight for pedagogy. Equally important are the learning principles of inclusion and social justice advanced by Culturally Relevant Pedagogy (CRP) educators such as Gloria Ladson-Billings (1992; 1995). Based on Halliday and Ladson-Billings premises, a bilingual English-Spanish adaptation of the SFL-based Reading to Learn (R2L) approach (Rose, 2018) is described through a curricular unit focusing on procedural texts in the context of an ESL family literacy program for immigrant Spanish-speaking mothers in Southeast USA. Informed by an adaptation of the preview-view-review bilingual curricular cycle to systematically use native and target language for content, genre, and language instruction, the article focuses on detailing R2L’s culturally and linguistically relevant curricular progression -Preparing to Read, Joint Construction, and Independent Construction-as well as the patterned language shifts that led these adult learners to produce rich genre-appropriate procedural texts in English. Crucially, this study proposes the adoption of Culturally and Linguistically Relevant Pedagogy (CLRP) through the use of ‘generative genres’ as a way to not only to counteract the current marginalization of CRP by standardized curriculum advanced by neoliberal imperatives (Sleeter, 2012) but as a way to better serve Emergent to Advanced Bilinguals (EABs) with an emphasis on adult English learners. The newly proposed CLRP paradigm is guided by core principles of CRP, but enhanced by linguistic principles and meaning making practices advanced by Systemic Functional Linguistics in general and genre-based pedagogy (Rose & Martin, 2012) and Halliday’s principles of learning language, learning through language, and learning about language in particular.
4D Printing via an Unconventional Fused Deposition Modeling Route to High-Performance Thermosets

An unprecedented four-dimensional (4D) printing process allowing high-performance and shape memory thermoset to be printed, for the first time, by fused deposition modeling (FDM) with isotropic properties has been achieved. Bisphenol A-based epoxy and benzoxazine were formulated to a low-temperature thermoplastic and high-temperature thermoset resin, which is melt-extrudable and can be postcured into covalently cross-linked material. Carbon nanotube (CNT) was added in the resin to work as both mechanical enhancement filler and rheology modifier to prevent shape deformation during postcuring process. The cross-layer reaction fuses individual layers into an integrity, thus eliminating layer delamination induced by FDM, offering isotropic mechanical properties regardless of the printing orientations. The highly cross-linked network provides outstanding mechanical strength and superb thermal stability. The excellent shape memory performance with fast recovery rate and large recovery degree is also obtained in the three-dimensional (3D) printed composites.
Chapter Nine - Frank Discussion of the Status of Ground-State Orbital-Free DFT

F.E. Harris has been a significant partner in our work on orbital-free density functional approximations for use in ab initio molecular dynamics. Here we mention briefly the essential progress in single-point functionals since our original paper (2006). Then we focus on the advantages and limitations of generalized gradient approximation (GGA) noninteracting kinetic energy (KE) functionals. We reconsider the constraints provided by near-origin conditions in atomic-like systems and their relationship to regularized versus physical external potentials. Then we seek the best empirical GGA for the noninteracting KE for a modest-sized set of molecules with well-defined near-origin behavior of their densities. The search is motivated by a desire for insight into GGA limitations and for a target for constraint-based development.
Materials with low DC magnetic susceptibility for sensitive magnetic measurements

Materials with very low DC magnetic susceptibility have many scientific applications. To our knowledge however, relatively little research has been conducted with the goal to produce a totally nonmagnetic material. This phrase in our case means after spatially averaging over macroscopic volumes, it possesses an average zero DC magnetic susceptibility. We report measurements of the DC magnetic susceptibility of three different types of nonmagnetic materials at room temperature: (I) solutions of paramagnetic salts and diamagnetic liquids, (II) liquid gallium–indium alloys and (III) pressed powder mixtures of tungsten and bismuth. The lowest measured magnetic susceptibility among these candidate materials is in the order of 10−9 cgs volume susceptibility units, about two orders of magnitude smaller than distilled water. In all cases, the measured concentration dependence of the magnetic susceptibility is consistent with that expected for the weighted sum of the susceptibilities of the separate components within experimental error. These results verify the well-known Wiedemann additivity law for the magnetic susceptibility of inert mixtures of materials and thereby realize the ability to produce materials with small but tunable magnetic susceptibility. For our particular scientific application, we are also looking for materials with the largest possible number of neutrons and protons per unit volume. The gallium–indium alloys fabricated and measured in this work possess to our knowledge the smallest ratio of volume magnetic susceptibility to nucleon number density per unit volume for a room temperature liquid, and the tungsten-bismuth pressed powder mixtures possess to our knowledge the smallest ratio of volume magnetic susceptibility to nucleon number density per unit volume for a room temperature solid. This ratio is a figure of merit for a certain class of precision experiments that search for possible exotic spin-dependent forces of Nature.
NIM: Modeling and Generation of Simulation Inputs Via Generative Neural Networks

We present Neural Input Modeling (NIM), a generative-neural-network framework that exploits modern data-rich environments to automatically capture simulation input distributions and then generate samples from them. Experiments show that our prototype architecture NIM-VL, which uses a novel variational-autoencoder architecture with LSTM components, can accurately, and with no prior knowledge, automatically capture a range of complex stochastic processes and efficiently generate sample paths. Moreover, we show that the outputs from a queueing model with (known) complex inputs are statistically close to outputs from the same queueing model but with the inputs learned via NIM. Known distributional properties such as i.i.d. structure and nonnegativity can be exploited to increase accuracy and speed. NIM can thus help overcome one of the key barriers to simulation for non-experts.
Asolo, the Creative Work of Memory

When in 1991 Countess Maria Fossi Todorow, the great granddaughter of Katharine deKay Bronson, made La Mura, the residence in Asolo, Italy, where Robert Browning spent two months of 1889, his last year, available to Robert Browning scholars and enthusiasts, it rekindled in them an interest in the tiny hilltop town that was the setting of Sordello and Pippa Passes and the place where the poet completed, proofed for the press and returned to his publisher, George Smith, his final collection Asolando. Now, to be able to climb the winding road to the city gate; walk the narrow streets of the walled medieval town — only slightly changed since Browning’s residence there; actually live in the quarters that the poet sometimes occupied; look down the Veneto plains and up toward the Alps from the Loggia of La Mura, built especially for him by Bronson; survey the remains of Queen Cornaro’s castle; visit La Rocca, the fortress on the highest point of the hill; view the silk factory where Pippa worked; and enter the Cathedral, the center point of the town, is to bring before us again the wonders of Browning’s early Italian obsession and his volumes Sordello, Pippa Passes and Asolando. That his poetic career should have ended with a residence in this ancient town, the place of his early poetic inspiration, is the supreme and marvelous coincidence of his remarkable career. Browning’s experience with the city — so overwhelming, so indelible — haunted him a near-lifetime: it became a repeated inspiration to him in his early years; its influence faded briefly at mid-career, then it was rekindled in his final year and became, as for his early works, the source and inspiration for his last collection.
Is Military Law Relevant to the 'Evolving Standards of Decency' Embodied in the Eighth Amendment?

On June 25, 2008, the United States Supreme Court issued an opinion in Kennedy v. Louisiana holding that the application of the death penalty to the crime of aggravated child rape violated the Eighth Amendment of the United States Constitution. Three days after the opinion was issued, it was discovered that everyone involved in the case had overlooked a 2006 amendment to the Uniform Code of Military Justice ("UCMJ") that made child rape a death penalty offense. This seeming oversight by the majority led the state of Louisiana and Solicitor General to petition the Court for the case to be reheard. On September 8, the Supreme Court took the highly unusual step of asking for more briefing on whether the case should be reheard. This short article contends that for the Court to grant rehearing based upon the rationales embodied in the Louisiana and Solicitor General's briefs would represent a substantial departure from past Court practice and be contrary to the special treatment that military law has historically received. A careful review of the Court's prior opinions shows that the Court has never considered military law in evaluating the objective indicia of the "evolving standards of decency" even when the military had seemingly relevant provisions. This practice by the Court is almost surely due to its recognition that when Congress amends military law, it only represents a national consensus as to military policy and not civilian policy. As a result, the Supreme Court should not rehear the Kennedy case based upon the majority opinion's omission of the 2006 UCMJ amendment.
Children in Diverse Families

Children in diverse families often have divergent life courses from children reared in other family forms. Diverse families, unlike first-marriage nuclear families, often are not formed by marriage, and when they are, the marriage may not be the first for at least one of the adults. Children in diverse families may be genetically related to only one parent or to neither parent. Diverse families may include more than two adults who serve in parental roles, or only one adult, not always a genetic parent, may be rearing children. Legal connections between parents and children, like genetic bonds, vary widely in diverse families. In this chapter we examine several types of diverse families as environmental contexts within which children develop: Families headed by unmarried and cohabiting parents, children who have had a parent die or whose parents have divorced, stepfamilies, families headed by gay and lesbian individuals, grandfamilies (grandparents raising grandchildren), and parents who utilized assisted reproductive technologies (ART). These categories are not homogeneous, so when feasible, we examine the state of the scholarship within subcategories of these larger family types. Keywords: assisted reproductive technology; childhood bereavement; cohabiting parents; divorce; family; family processes; family structure; gay parents; grandparents and grandchildren; lesbian parents; parent-child relationships; single parents; stepchildren; stepfamilies; stepparents; unmarried parents
The Voice and Masculinity, on Close Up: Cinema and Modernism 1927-1933, edited by James Donald, Anne Friedberg, and Laura Marcus

_Close Up: Cinema and Modernism 1927-1933_ Edited by James Donald, Anne Friedberg, and Laura Marcus London: Cassell, 1998 ISBN 0-304-33516-9 341pp.
Packaging of micro strain sensors

This paper presents results of studies on the packaging of micro strain sensors attached to a stainless steel base as a module and techniques of rapid attachment of sensor modules to substrates to be measured. Strain coupling from the substrate to the sensors using different packaging designs and processes can either enhance or attenuate strains experienced by the sensors. Analytical models were developed to predict the enhancement and transmission loss from the packaging materials and processes used. Experiments were carried out with results verifying that the analysis is accurate to a few percentages of assumed properties. Rapid bonding techniques were developed, which combine spot welding and adhesive bonding with selected bonding materials, to bond pre-packaged sensor modules to substrates in 30 seconds instead of hours as in conventional methods.
Intelligence and Risk Management

This paper summarizes a two-year project working with risk management specialists in finance, health care, political risk, engineering, and other fields to understand how risk management applies to intelligence and international security affairs. It distinguishes between two broad approaches for risk management implementation in complex organizations (large companies, the U.S. intelligence community). Tactical approaches focus on particular models (VaR, option theory, fault trees, etc.) while strategic approaches take an enlarged view of key managerial and contextual factors which shape the actual use of risk management. As environments become more turbulent, managers should focus far more on these strategic, rather than tactical approaches to managing risk.