Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma

Many studies support a stepwise continuum of morphologic changes between atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma (ADC). Here we characterized gene expression patterns and the association of differentially expressed genes and immune tumor microenvironment behaviors in AAH to ADC during ADC development. Tumor tissues from nine patients with ADC and synchronous multiple ground glass nodules/lesions (GGN/Ls) were analyzed using RNA sequencing. Using clustering, we identified genes differentially and sequentially expressed in AAH and ADC compared to normal tissues. Functional enrichment analysis using gene ontology terms was performed, and the fraction of immune cell types was estimated. We identified up-regulated genes (ACSL5 and SERINC2) with a stepwise change of expression from AAH to ADC and validated those expressions by quantitative PCR and immunohistochemistry. The immune cell profiles revealed increased B cell activities and decreased natural killer cell activities in AAH and ADC. A stepwise change of differential expression during ADC development revealed potential effects on immune function in synchronous precursors and in tumor lesions in patients with lung cancer.

DYNAMICS OF THE TEMPERATURE SENSOR OF THE «SMART HOME» HEATING SYSTEM

The article deals with the issues of modeling the control of room heating. The dynamics of the object-the heating system of a residential building-is obtained. The equation of the dynamics of the temperature sensor is derived. Dynamic errors are determined by the dynamic characteristics of the temperature sensor. The dynamic error is determined for a stepwise change in the input signal.

Energy characteristics of acoustic emission under various modes of uniaxial loading

Acoustic emissions were recorded in the process of uniaxial compression of samples of various geomaterials. The experiments were carried out on a low-noise lever setup with water leakage; the maximum load on the sample did not exceed 250 kN. Some of the samples were tested at a continuously increasing load, the other at its stepwise change. The energy distribution of acoustic emission signals was investigated. The energy characteristic of acoustic emission was the square of the maximum signal amplitude. The flow of AE events is considered from the standpoint of nonequilibrium thermodynamics and Tsallis statistics. A decrease in the steepness of the linear part of the repeatability plots for a particular geomaterial was revealed when changing the loading mode from linear to stepwise, which means an increase in the proportion of higher-energy events with a stepwise change in load.

Concept of an In-Plane Displacement Sensor Based on Grating Interferometry with a Stepwise Change of Sensitivity

Grating Interferometry, known in the relevant literature as the High Sensitivity Moiré Interferometry, is a method for in-plane displacement and strain measurement. The sensitivity of this method depends on the spatial frequency of the diffraction grating attached to the object under test. For typical specimen grating, with high spatial frequency of 1200 lines per mm, the basic sensitivity is 0.417 µm per fringe. A concept of in-plane displacement sensor based on Grating Interferometry with a stepwise change in sensitivity is presented. It is realized by using the specimen grating with lower spatial frequency. In this case, the grating has more higher diffraction orders and by selecting them appropriately, the sensitivity (chosen from 1.25 μm, 0.625 μm, or 0.417 μm) and the resulting measurement range (chosen from about 600 μm, 300 μm, or 200 μm) can be adjusted to the requirements of a given experiment. A special method of filtration is required in this case. Achromatic configuration with illumination grating was chosen due to its low sensitivity to vibration.

Impact of homeometric autoregulation using a stepwise change in heart rate on dP/dtmax and time to peak dP/dt with resynchronization therapy

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South East heath Authorities Background We investigated the homeometric autoregulation utilizing a stepwise change in heart rate on dP/dtmax and time to peak dP/dt (Td) with biventricular pacing (BIVP) and the LV lead positioned in the apical, anterior and lateral positions. Pacing at low HR (LHR) and high heart rates (HHR) changes contractility through homeometric autoregulation (Bowditch effect) without changing the resynchronization itself. Purpose To determine the effect of a change in contractility through homeometric autoregulation on two different effect measures of resynchronization therapy. Methods Twenty-nine patients in heart failure with LBBB underwent CRT implantation with continuous LV pressure registration. The LV lead was first placed in either apical or anterior position followed by a permanent placement in a lateral position. Sequential BIVP pacing was performed for one minute, at a rate 10% above intrinsic heart rate (LHR = 75 ± 9bpm), before dP/dtmax measurements were recorded, and the sequence was repeated with pacing rate increased by 30% (HHR = 98 ± 11bpm). Td was defined as the time from pacemaker stimuli to peak dP/dt. Mixed linear models were used for statistics, numbers are estimated marginal means ± SEM. Significance was set at p < 0.05. Results DP/dtmax was higher with HHR in lateral position (1036 ± 41mmHg/s) than with LHR (933mmHg/s). The same was observed for all other lead positions. However, there was no difference between lateral position with LHR and apical position with HHR (930 ± 44mmHg/s). There were no differences in Td between LHR and HHR, but Td was shorter with BIVP in lateral position at pacing LHR (158 ± 4ms) and HHR (155 ± 4ms) than in all other positions. Overall dP/dtmax increased by 10% from LHR to HHR (888 ± 41mmHg/s vs. 980 ± 41 mmHg/s), while overall Td decreased by 2.4% from 168 ± 4ms to 164 ± 4ms. We found a linear relationship between Td and dP/dtmax (R = 0.7) with β=-0.07 that would indicate a 6ms reduction in Td going from LHR to HHR. The overall change in Td from LHR to HHR could therefore be attributed to the change in dP/dtmax. Conclusion Homeometric regulation does not influence Td, but Td is sensitive to changes in resynchronization and pacing lead position. Td is shorter with BIVP in lateral position at both high and low HR as would be expected from a biomarker of resynchronization. HR influences dP/dtmax so distinction between optimal and non-optimal positions using dP/dtmax may be difficult without knowledge of homeometric state.

Simulated controlled-release mesotrione for turfgrass tolerance and weed control

Mesotrione typically requires multiple applications to control emerged weeds in turfgrass. Since it is absorbed by both foliage and roots, a controlled-release (CR) formulation could eliminate the need for multiple applications. Research was conducted evaluate simulated-release scenarios that mimic a potential CR mesotrione formulation. A soluble concentrate formulation of mesotrione was titrated to produce a stepwise change in mesotrione rates, which were applied daily to mimic predetermined release scenarios over a three-wk period. CR scenarios were compared to a broadcast treatment of mesotrione at 280 g ai ha-1 applied twice at three-wk intervals, and a nontreated. Mesotrione applied in three temporal release scenarios controlled creeping bentgrass, goosegrass, nimblewill, smooth crabgrass, and white clover equivalent to the standard sprayed mesotrione treatment in every comparison. However, each CR scenario injured tall fescue 2 to 7 times more than the standard treatment. Soil- and foliar-initiated repeat treatments were equivalent in most comparisons. Data indicates that mesotrione applied in a temporal range to simulate controlled release scenarios can deliver desired weed control efficacy comparable to sequential broadcast applications. More research is needed to elucidate proper timings and release scenarios to minimize turfgrass injury.

Transitional evolutionary forms in chasmosaurine ceratopsid dinosaurs: evidence from the Campanian of New Mexico

Three new chasmosaurines from the Kirtland Formation (~75.0–73.4 Ma), New Mexico, form morphological and stratigraphic intermediates between Pentaceratops (~74.7–75 Ma, Fruitland Formation, New Mexico) and Anchiceratops (~72–71 Ma, Horseshoe Canyon Formation, Alberta). The new specimens exhibit gradual enclosure of the parietal embayment that characterizes Pentaceratops, providing support for the phylogenetic hypothesis that Pentaceratops and Anchiceratops are closely related. This stepwise change of morphologic characters observed in chasmosaurine taxa that do not overlap stratigraphically is supportive of evolution by anagenesis. Recently published hypotheses that place Pentaceratops and Anchiceratops into separate clades are not supported. This phylogenetic relationship demonstrates unrestricted movement of large-bodied taxa between hitherto purported northern and southern provinces in the late Campanian, weakening support for the hypothesis of extreme faunal provincialism in the Late Cretaceous Western Interior.

A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic

STUDY QUESTION Is a stepwise change management approach an efficacious method to move from a Day 3 transfer policy to a Day 5 transfer policy for all patients in an IVF program? SUMMARY ANSWER A stepwise change from a Day 3 to a Day 5 transfer policy maintained the live birth rates per oocyte collection cycle (OCC) of the IVF program, with increased single embryo transfer (SET) and reduction of twin pregnancies. WHAT IS KNOWN ALREADY Evidence has shown that the probability of a live birth following IVF with a fresh embryo transfer (ET) is significantly higher after blastocyst-stage transfer than after cleavage-stage transfer. Blastocyst culture and transfer are usually performed in cases of good prognosis patients but many centers keep transferring cleavage-stage embryos for most of their patients because of the higher transfer cancelation rate in a blastocyst transfer policy. STUDY DESIGN, SIZE, DURATION In January 2012, a Day 5 embryo culture and blastocyst transfer policy including vitrification of supernumerary Day 5 blastocysts were implemented in a stepwise approach. The retrospective descriptive single-center analysis involving a preintervention phase consisted of Day 3 ETs and Day 3 slow freezing from 2010 until 2012. The postintervention phase involved a 6-year period from 2012 until 2017 in which three consecutive changes in the transfer policy were made, each over a 2-year period, based on the number of zygotes on Day 1. The primary outcome was live birth delivery rate per OCC during the stepwise change. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients with at least one zygote available on Day 1 were scheduled for a fresh transfer, either on Day 3 or 5. Cycles with preimplantation genetic testing, freeze-all and oocyte donation cycles and cycles with a Day 2 transfer in the preintervention period were excluded. In the preintervention group, all cycles were scheduled for Day 3 transfer (n = 671 OCC) and slow freezing of the remaining Day 3 embryos. In the postintervention period, three periods were analyzed: period 1 (n = 1510 OCC; 1–9 zygotes: Day 3 transfer and >9 zygotes: Day 5 transfer); period 2 (n = 1456 OCC; 1–4 zygotes: Day 3 transfer and >4 zygotes: Day 5 transfer) and period 3 (n = 1764 OCC; Day 5 transfer). All remaining embryos underwent extend culture and were vitrified on Day 5, if developed to at least an early blastocyst. Data were analyzed using a mixed regression model with patient as a random factor. MAIN RESULTS AND THE ROLE OF CHANCE In the preintervention group, all OCC were scheduled for a Day 3 transfer. In period 1, period 2 and period 3, 20.9%, 61.5% and 100% of the OCCs were scheduled for a Day 5 transfer, respectively. More transfers per OCC were canceled in the postintervention period 2 and period 3 compared to the preintervention period (5.3% and 18.7% versus 3.4%, respectively; P < 0.0001). The mean number of embryos used per transfer decreased gradually after the introduction of the Day 5 transfer policy, from 1.62 ± 0.65 in the preintervention group to 1.12 ± 0.61 in period 3 (P < 0.0001). The percentage of SET cycles increased from 48.4% in the preintervention group to 54.6%, 73.8% and 87.8% in period 1, period 2 and period 3, respectively (P < 0.0001). The mean number of cryopreserved surplus embryos was significantly lower in period 3 compared to the preintervention group (1.29 ± 1.97 versus 1.78 ± 2.80; P < 0.0001). Pregnancy and live birth delivery rate per fresh transfer, respectively, were significantly lower in the preintervention group (26.7% and 19.1%) as compared to period 3 (39.3% and 24.2%) (P < 0.0001). Twin pregnancy rate decreased gradually from 11.0% to 8.2%, 5.7% and 2.5% in the preintervention group, period 1, period 2 and period 3, respectively (P < 0.0001). Live birth rate and cumulative live birth delivery rates per OCC were significantly higher in group 2 compared to the preintervention period (25.6% and 35.8% versus 18.5% and 25.9%, respectively). Similar live birth and cumulative live birth delivery rates per OCC were achieved between the preintervention period and period 3 (18.5% and 25.6% versus 19.7% and 24.9%; respectively). LIMITATIONS, REASONS FOR CAUTION The primary limitation is the retrospective design of the study. The allocation of the cycles was done by the number of zygotes available without taking into account both embryological and clinical prognostic factors. Furthermore, the analysis was restricted to cycles where the standard transfer policy was followed. Embryos which were in the morula or compaction stage were not vitrified or cultured to Day 6, which could have contributed to the slight, not statistically significant, drop in live birth rate per OCC in group 3. WIDER IMPLICATIONS OF THE FINDINGS Live birth and cumulative live birth delivery rate per OCC in an unselected patient population is maintained in a Day 5 transfer policy compared to a Day 3 transfer policy. Additionally, a significantly reduction in twin pregnancy rate and a significant increase in SET were observed in a Day 5 transfer policy. For centers wanting to make the step from Day 3 to Day 5, this study provides a practical stepwise change management approach. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER None.

Step-by-step: uncommon SCSC transformation accompanied by stepwise change in the binding of a particular ligand within a mononuclear complex upon stepwise desolvation

Uncommon SCSC transformation when desolvation induces subtle changes within a mononuclear complex, namely a stepwise change in the binding of a particular ligand.