Miracle-dz/UniFAR-FTUs huggingface dataset:
Butterfly Selected Lines Explore the Hormonal Basis of Interactions between Life Histories and Morphology

Hormonal mechanisms underlie many life‐history traits and their interactions. We studied the role of ecdysteroids with regard to wing pattern and development time of the polyphenic butterfly Bicyclus anynana. Ecdysteroid titers and sensitivity to ecdysone injection were assayed for two‐trait selected lines (ventral eyespot size and development time concurrently). These two traits are genetically and phenotypically coupled, having a common endocrinal basis. Two‐trait selection had been applied both antagonistically (opposite the correlation) and synergistically (in the same direction as the correlation). Although selected lines had diverged most in eyespot size, the widest differences in timing of ecdysteroid titers were observed between the development time selection regimes; fast selected lines had an earlier hormonal increase after pupation than slow selected lines (even when corrected for differential pupal times). This endocrine peak was also earlier for females than for males. Furthermore, sensitivity to ecdysone injection as measured by a subsequent decrease in pupal time was significantly lower for slow selected lines than for fast or unselected lines. We conclude that the observed response in eyespot size to artificial selection must have been achieved via alteration of, or selection on, other developmental mechanisms, because the dynamics of the alternative, hormonal, pathway were dictated by development time selection. The developmental system is flexible enough to allow evolution in directions opposing the correlation between wing pattern and developmental time, and responses to selection are not constrained by a shared hormonal system.
Nocturnal Oviposition Behavior of Forensically Important Diptera in Central England

Timing of oviposition on a corpse is a key factor in entomologically based minimum postmortem interval (mPMI) calculations. However, there is considerable variation in nocturnal oviposition behavior of blow flies reported in the research literature. This study investigated nocturnal oviposition in central England for the first time, over 25 trials from 2011 to 2013. Liver‐baited traps were placed in an urban location during control (diurnal), and nocturnal periods and environmental conditions were recorded during each 5‐h trial. No nocturnal activity or oviposition was observed during the course of the study indicating that nocturnal oviposition is highly unlikely in central England.
Effects of Proximal Ventricular Septal Pacing on Hemodynamics and Ventricular Activation

Recently the use of alternate site pacing to improve cardiac function in patients with bradyarrhythmias has increased. In the present study, hemodynamics of right ventricular septal pacing were studied in seven dogs. A bipolar screw‐in lead and endocardial lead were placed in the proximal right ventricular septum and right ventricular apex, respectively. The right ventricle was paced from each site. A conductance catheter and Millar catheter were inserted into the left ventricle to determine the left ventricular pressure and the pressure–volume loop. Cardiac output was measured using the thermodilution method. In five of the seven dogs, ventricular activation was documented by isochronal epicardial activation mapping during each pacing mode. Mean arterial pressure and cardiac output during septal pacing were significantly higher than during apical pacing (110 ± 17 mmHg vs 100 ± 18 mmHg; 1.00 ± 0.39 L/min vs 0.89 ± 0.33 L/min). The positive dp/dt during septal pacing was significantly higher than during apical pacing (2137 ± 535 mmHg/s vs 1911 ± 404 mmHg/s). End‐systolic elastance during septal pacing was significantly higher compared to apical pacing (13.1 ± 0.3 mmHg/mL vs 8.9 ± 4.0 mmHg/mL). The ventricular activation time during septal pacing was significantly shorter than during apical pacing. The epicardial maps generated during septal pacing were similar to those from atrial pacing. We conclude that hemodynamics and interventricular conduction are less disturbed by proximal right ventricular septal pacing than apical pacing in dogs with normal hearts.
Angiotensin II potentiates DNA synthesis in AT-1 transformed cardiomyocytes.

Angiotensin II has been shown to be mitogenic in various cell types. In cultured neonatal cardiomyocytes, we have demonstrated that angiotensin II causes hypertrophy, not hyperplasia. However, fetal or neonatal cardiomyocytes exhibit limited proliferation in primary culture, and are mitotically less potent. In order to determine whether angiotensin II is simply a hypertrophic or hyperplastic growth factor for mitotically-potent cardiomyocytes, we analysed [3H]-thymidine uptake and cell cycle-regulated gene expression using SV40 large T-transformed AT-1 cardiomyocytes. Angiotensin II, alone and in combination with other growth factors, increased [3H]-thymidine uptake in a dose-dependent manner. The mRNA expression of G1 cyclins (Cyclin C, D1, D2, D3) and histone H1-kinase activity by CDK2 increased 6 h after angiotensin II stimulation. Western blot analysis revealed cyclin B1 expression after 18 h , which peaked at 30 h. Histone H1-kinase activity by cdc2 was also increased by angiotensin II, and peaked at 24-36 h, indicating that these changes were cell cycle dependent. Double immunofluorescent photography showed that AT-1 cells incorporated BrdU, and expressed cdc2 by angiotensin II stimulation. [3H]-thymidine and BrdU uptake were blocked by losartan, but not by PD123319. In contrast with neonatal cardiomyocytes, angiotensin II potentiated DNA synthesis and induced cell cycle regulated gene expression in AT-1 cardiomyocytes, and this activity was mediated by the angiotensin II type-1 receptor.
TGF‐β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward Nucleus Pulposus‐like Cells

Degenerative disc disease (DDD) primarily affects the central part of the intervertebral disc namely the nucleus pulposus (NP). DDD explains about 40% of low back pain and is characterized by massive cellular alterations that ultimately result in the disappearance of resident NP cells. Thus, repopulating the NP with regenerative cells is a promising therapeutic approach and remains a great challenge. The objectives of this study were to evaluate the potential of growth factor‐driven protocols to commit human adipose stromal cells (hASCs) toward NP‐like cell phenotype and the involvement of Smad proteins in this differentiation process. Here, we demonstrate that the transforming growth factor‐β1 and the growth differentiation factor 5 synergistically drive the nucleopulpogenic differentiation process. The commitment of the hASCs was robust and highly specific as attested by the expression of NP‐related genes characteristic of young healthy human NP cells. In addition, the engineered NP‐like cells secreted an abundant aggrecan and type II collagen rich extracellular matrix comparable with that of native NP. Furthermore, we demonstrate that these in vitro engineered cells survived, maintained their specialized phenotype and secretory activity after in vivo transplantation in nude mice subcutis. Finally, we provide evidence suggesting that the Smad 2/3 pathway mainly governed the acquisition of the NP cell molecular identity while the Smad1/5/8 pathway controlled the NP cell morphology. This study offers valuable insights for the development of biologically‐inspired treatments for DDD by generating adapted and exhaustively characterized autologous regenerative cells. Stem Cells 2016;34:653–667
The point of no return in vetoing self-initiated movements

Significance Many studies have shown that movements are preceded by early brain signals. There has been a debate as to whether subjects can still cancel a movement after onset of these early signals. We tested whether subjects can win a “duel” against a brain–computer interface designed to predict their movements in real time from observations of their EEG activity. Our findings suggest that subjects can exert a “veto” even after onset of this preparatory process. However, the veto has to occur before a point of no return is reached after which participants cannot avoid moving. In humans, spontaneous movements are often preceded by early brain signals. One such signal is the readiness potential (RP) that gradually arises within the last second preceding a movement. An important question is whether people are able to cancel movements after the elicitation of such RPs, and if so until which point in time. Here, subjects played a game where they tried to press a button to earn points in a challenge with a brain–computer interface (BCI) that had been trained to detect their RPs in real time and to emit stop signals. Our data suggest that subjects can still veto a movement even after the onset of the RP. Cancellation of movements was possible if stop signals occurred earlier than 200 ms before movement onset, thus constituting a point of no return.
[The effect and mechanism of microRNA-21 on cis-dichlorodiamineplatinum resistance in lung cancer cell strain].

OBJECTIVE To investigate the role of miR-21 on multidrug resistance (MDR) in non-small cell lung cancer(NSCLC)and to provide experimental and theoretical basis for MDR reversal. METHODS Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to determine the mRNA level of miR-21 both in the chemo-sensitivity cell strain A549 and the chemo-resistance cell strain A549/DDP (primary A549/DDP cells). The miR-21 interference sequence was synthesized and transfected into A549/DDP cells by liposome as the carrier. The miR-21 expression level was knocked down and the change of chemo-sensitivity of cells was detected. Effects of miR-21 on the cell apoptosis and cell cycle in miR-21-depleted A549/DDP cells were analyzed by flow cytometry to elucidate the involvement of miR-21 in MDR reversal in NSCLC. The expression of multidrug-resistant proteins Survivin, Cyclin D1, Epidermal growth factor receptor (EGFR), Multidrug resistance-associated protein1 (MRP1) and Lipoprotein receptor-related protein (LRP) were detected by Western blot. RESULTS MiR-21 level in multidrug-resistant NSCLC cell line A549/DDP was (5.223±0.316) folds higher than that in A549 cell line (t=48.318, P<0.01). Knockdown of miR-21 in A549/DDP cells significantly reversed their sensitivity to cis-DDP, meanwhile, the value of half maximal inhibitory concentration was significantly decreased compared with control group transfected with empty vector ((22.2±1.2) and (48.6±3.2) μmol/L, t=5.608, P<0.01). Cell apoptosis rate in A549/DDP cell with knockdown of miR-21 was significantly increased compared with primary A549/DDP cell line ((27.7±1.1) % and (16.8±1.1) %, t=10.183, P<0.01). Cell cycle G0/G1 phase in A549/DDP cell with knockdown of miR-21 was significantly decreased compared with primary A549/DDP cell line ((37.5±1.2) % and (43.4±2.3) %, t=8.202, P<0.01). Compared with primary A549/DDP cell line, the expression of Survivin, Cyclin D1, EGFR, MRP1 and LRP in A549/DDP cell with knockdown of miR-21 were significantly decreased ((71.7±4.3)%, t=8.325, P<0.01; (69.4±4.5)%, t=5.162, P<0.01; (52.3±3.2)%, t=8.042, P<0.01; (60.6±4.2)%, t=6.641, P<0.01; (72.9±3.8)%, t=4.566, P<0.01, respectively). CONCLUSION miR-21 silencing reverses the multidrug resistance in lung cancer cell via accelerating cell apoptosis and modulating multidrug resistance-related gene expression. miR-21 may be a potential therapeutic candidate in multidrug resistance patients with lung cancer.
A new low voltage swing gate driver for integrated buck converter with synchronous rectifier

This paper presents a new low-swing gate-driver for a buck converter. In the proposed gate drive technique, the converter output voltage is used to supply gate driver. Also, by controlling gate pulses properly, energy recycling is achieved and efficiency is improved. In addition, zero voltage switching condition is achieved for front-end switches which results in reduced switching power losses. To overcome converter start up problem, a simple circuit which consists of two diode-connected NMOS are used to pre-charge the converter output capacitor. This circuit does not have any effect on the converter output voltage at steady state operation. Since the output voltage is used for supplying the switch driver, the converter can operate with smaller supply voltages and also the efficiency is improved. A prototype with switching frequency of 660MHz in 0. 18μm CMOS technology is simulated and simulation results verify the operation principles and design procedure.
Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials.

OBJECTIVE To compare the incidence of anti-double-stranded DNA (anti-dsDNA) antibodies in rheumatoid arthritis (RA) patients receiving either single or multiple doses of a chimeric anti-tumor necrosis factor alpha (anti-TNFalpha) antibody or placebo infusions, with or without methotrexate, in open-label, randomized, placebo-controlled trials. METHODS Multiple sera obtained from 156 patients before and after treatment with infliximab and from 37 patients treated with placebo infusions were tested for anti-dsDNA antibodies by 3 methods: Crithidia luciliae indirect immunofluorescence test (CLIFT), a commercial Farr assay (Ortho Diagnostics radioimmunoassay [RIA]) in which the antigen source is mammalian DNA, and a Farr assay employing 125I-labeled circular plasmid DNA (Central Laboratory of The Netherlands Red Cross Blood Transfusion Service [CLB] RIA). Patients with positive findings on the CLIFT were also tested for antibodies to histones (H1-H5) and chromatin and for IgM rheumatoid factors (IgM-RFs). RESULTS None of the RA patients had a serum sample that was positive for anti-dsDNA antibodies by the CLIFT prior to infliximab therapy. Of the 22 patients who developed a positive CLIFT result, 11 (7% of 156 exposed to infliximab) also had positive findings on the Ortho RIA at a concentration of >10 units/ml and another 8 (5%) were positive at a concentration of >25 units/ml. In all but 1 patient, the anti-dsDNA antibodies were solely of the IgM isotype. Only 1 patient had detectable anti-dsDNA antibodies by the CLB RIA. All sera containing anti-dsDNA by the CLIFT contained antibodies to chromatin, and sera from 2 patients also contained antibodies to histones. IgM-RF titers showed a significant reduction following infliximab therapy in these 22 patients. One patient developed anti-dsDNA antibodies of IgG, IgA, and IgM isotype and had positive results on both Farr assays (peaking at 22 weeks and resolving by 54 weeks); this was associated with a reversible lupus syndrome. CONCLUSION Anti-dsDNA antibodies of IgM class are induced by infliximab therapy; the frequency is dependent on the assay method used. Only 1 of the 156 patients who were treated with infliximab developed a self-limiting clinical lupus syndrome; that patient developed high titers of anti-dsDNA antibodies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 different Farr assays.
Fetoplacental angiogenesis during gestation is biphasic, longitudinal and occurs by proliferation and remodelling of vascular endothelial cells.

Villous development and maturation depend on fetoplacental angiogenesis but detailed baseline quantitative data on underlying structural events are lacking. The present aim was to analyse temporospatial patterns of villous and fetal vascular growth using microscopical sections of placentae at different periods of gestation. The emphasis is on acquiring absolute rather than relative data. Random tissue samples collected at 10-41 weeks of gestation were processed for stereological analyses. Growth strategies in 'stem', 'intermediate' and 'terminal' villi (classified according to villous diameter and nature of fetal vessels) were evaluated in terms of total volumes, lengths and mean cross-sectional areas. Total volume, total and relative length, mean cross-sectional area and shape, vascular endothelial cell number and mean cell size (squame surface area) were used to examine capillary growth. Volumes of 'intermediate' and 'terminal' villi increased significantly due to elongation and thinning. Villous maturation involved differential growth of capillaries which grew linearly without changes in mean cross-sectional area. Longitudinal growth was due to endothelial cell proliferation and increases in mean cell area. Events were characterized by a common inflection point at about mid-gestation. Usually, an early slow growth phase was followed by one of faster growth but capillary : villus length ratios and capillary shape factors tended to peak at mid-gestation. Findings confirm that angiogenesis is linked to villous growth and maturation, and is biphasic with dramatic changes in vascular content and arrangement occurring around mid-gestation. Capillary growth occurs preferentially and is solely by increase in total length driven by continuous proliferation and, later, by endothelial cell remodelling. Though providing no evidence for branching versus non-branching angiogenesis, these observations are consistent with the paradigm that fetoplacental angiogenesis occurs in two phases, the switch being associated with changes in uteroplacental oxygen tensions, local growth factor receptors and their ligands.
El análisis económico del derecho en Latinoamérica. Algunos aspectos éticos reconsiderados

In Latin America, law and economics scholarship is gradually finding its way into court decisions and legislative enactments, both with respect to an increasing tendency to assess the overall consequences of legal rules, in terms of a growing application of cost-benefit analyses, and in the form of more incentives-driven reasoning. Until today, however, the literature on the movement’s normative foundations has failed to find common ground on how to justify its theoretical suppositions. This article illuminates this debate and provides an overview over some of the approach’s most basic assumptions that relate to its positive and normative implications.
Single‐Center Kidney Paired Donation: The Methodist San Antonio Experience

Many potential kidney transplant recipients are unable to receive a live donor transplant due to crossmatch or blood type incompatibility. Kidney paired donation increases access to live donor transplantation but has been significantly underutilized. We established a kidney paired donation program including consented incompatible donor/recipient pairs as well as compatible pairs with older non‐human leukocyte antigen identical donors. Over a 3‐year period, a total of 134 paired donor transplants were performed, including 117 incompatible pairs and 17 compatible pairs. All transplants were done with negative flow cytometry crossmatches and five were done with desensitization combined with paired donation. Kidney paired donation transplants included two‐way and three‐way exchanges as well as three chains initiated by nondirected donors. Of the sensitized recipients transplanted by paired donation, 44% had calculated panel reactive antibody levels greater than 80%. Transplantation of females and prior transplant recipients was significantly higher with paired donation. Only three episodes of rejection occurred and no transplants were lost due to rejection. These data highlight the potential of kidney paired donation and suggest that all transplant centers should be actively engaged in paired donation to increase access to live donor transplantation.
Association between nurse-physician collaboration and patient outcomes in three intensive care units.

OBJECTIVE To investigate the association of collaboration between intensive care unit (ICU) physicians and nurses and patient outcome. DESIGN Prospective, descriptive, correlational study using self-report instruments. SETTINGS A community teaching hospital medical ICU, a university teaching hospital surgical ICU, and a community non-teaching hospital mixed ICU, all in upstate New York. SUBJECTS Ninety-seven attending physicians, 63 resident physicians, and 162 staff nurses. PROCEDURE When patients were ready for transfer from the ICU to an area of less intensive care, questionnaires were used to assess care providers' reports of collaboration in making the transfer decision. After controlling for severity of illness, the association between interprofessional collaboration and patient outcome was assessed. Unit-level organizational collaboration and patient outcomes were ranked. MEASURES Healthcare providers' reported levels of collaboration, patient severity of illness and individual risk, patient outcomes of death or readmission to the ICU, unit-level collaboration, and unit patient risk of negative outcome. MAIN RESULTS Medical ICU nurses' reports of collaboration were associated positively with patient outcomes. No other associations between individual reports of collaboration and patient outcome were found. There was a perfect rank order correlation between unit-level organizational collaboration and patient outcomes across the three units. CONCLUSIONS The study offered some support for the importance of physician-nurse collaboration in ICU care delivery, a variable susceptible to intervention and further study.
Localized fluidization burrowing mechanics of Ensis directus

SUMMARY Muscle measurements of Ensis directus, the Atlantic razor clam, indicate that the organism only has sufficient strength to burrow a few centimeters into the soil, yet razor clams burrow to over 70 cm. In this paper, we show that the animal uses the motions of its valves to locally fluidize the surrounding soil and reduce burrowing drag. Substrate deformations were measured using particle image velocimetry (PIV) in a novel visualization system that enabled us to see through the soil and watch E. directus burrow in situ. PIV data, supported by soil and fluid mechanics theory, show that contraction of the valves of E. directus locally fluidizes the surrounding soil. Particle and fluid mixtures can be modeled as a Newtonian fluid with an effective viscosity based on the local void fraction. Using these models, we demonstrate that E. directus is strong enough to reach full burrow depth in fluidized soil, but not in static soil. Furthermore, we show that the method of localized fluidization reduces the amount of energy required to reach burrow depth by an order of magnitude compared with penetrating static soil, and leads to a burrowing energy that scales linearly with depth rather than with depth squared.
TCR-Mediated Up-Regulation of c-FLIPshort Correlates with Resistance Toward CD95-Mediated Apoptosis by Blocking Death-Inducing Signaling Complex Activity1

To investigate apoptosis resistance upon restimulation in human peripheral blood T lymphocytes, we used the following in vitro model. This model represents the main features of T cell reactivity: freshly isolated PHA-activated T cells cultured in IL-2 for a prolonged period of time develop a CD95 (APO-1/Fas) apoptosis-sensitive phenotype. These T cells represent activation-induced cell death-sensitive T cells during the down phase of an immune response. A fraction of apoptosis-sensitive activated T cells becomes apoptosis resistant upon TCR/CD3 restimulation. CD95 apoptosis sensitivity requires formation of a functional receptor associated death-inducing signaling complex (DISC), i.e., a protein complex of CD95 receptors, the adaptor Fas-associated death domain protein (FADD)/MORT1 and caspase-8 (FADD-like IL-1β-converting enzyme (FLICE), MACH, Mch5). We identified activation of procaspase-8 at the DISC as the main target for the protective activity of TCR/CD3 restimulation. We found that procaspase-8 cleavage is reduced in T cells after TCR/CD3 restimulation. In addition, we detected up-regulation of c-FLIPS (the short splice variant of the cellular FLICE inhibitory protein) and strongly enhanced recruitment of c-FLIPS into the DISC. These data suggest that the recruitment of c-FLIPS into the DISC results in reduced DISC and caspase-8 activity.