Prolonged Window Research Articles

Effectiveness of natural ventilation through single-sided window opening in air-conditioning rooms

Since many buildings are not equipped with fresh air systems, many people open windows to allow for natural ventilation while the air conditioner is running. However, prolonged window opening may cause unnecessary energy consumption. Additionally, the diverse ways of window opening lead to significant variations in indoor airflow distribution, consequently impacting ventilation efficiency. Therefore, this study used field experiments and computational fluid dynamics (CFD) to determine the air exchange efficiency and air change rate of single-sided natural ventilation in air-conditioning rooms by fitting the decay curves of tracer gas. CFD simulation was performed using the unsteady Reynolds-averaged Navier-Stokes (RANS) model to examine how window openings affect the room’s air distribution, and the computed indoor CO2 concentration was compared to the corresponding field experiment data. The results show that natural ventilation through the window opening induced constant heat and mass exchange between indoor and outdoor air, which caused extra cooling losses but was globally effective in eliminating indoor contaminants. The air exchange efficiency is influenced to varying degrees by factors such as the air supply register’s position, window opening percentage, and window opening position. The air supply register’s position exerted the most significant impact at 46.45%. Efficient indoor-outdoor air exchange can be achieved by opening windows intermittently. When the window is opened from one side and the opening percentage is 100%, the indoor environment can be improved by opening the window for about 10 min every 39 min for X-direction air supply and about 7 min every 39 min for Y-direction.

CD38 regulates ovarian function and fecundity via NAD+ metabolism

Mammalian female reproductive lifespan is typically significantly shorter than life expectancy and is associated with a decrease in ovarian NAD+ levels. However, the mechanisms underlying this loss of ovarian NAD+ are unclear. Here, we show that CD38, an NAD+ consuming enzyme, is expressed in the ovarian extrafollicular space, primarily in immune cells, and its levels increase with reproductive age. Reproductively young mice lacking CD38 exhibit larger primordial follicle pools, elevated ovarian NAD+ levels, and increased fecundity relative to wild type controls. This larger ovarian reserve results from a prolonged window of follicle formation during early development. However, the beneficial effect of CD38 loss on reproductive function is not maintained at advanced age. Our results demonstrate a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing the ovarian reserve, a critical process that dictates a female's reproductive lifespan.

0779 Impact of 8-h Time Limited Eating on Sleep in Adolescents with Obesity

Abstract Introduction Time-based interventions, such as time-limited eating (TLE), have become a promising dietary strategy in adults with obesity. TLE involves shortening the daily eating window to a pre-specified number of hours and fasting for the remaining hours of the day without altering diet quality. No study to date has examined the impact of TLE on sleep quality in adolescents with obesity. Methods We conducted a secondary analysis of a 12-week pilot study that compared TLE (8-h eating window/16-h fasting window) to a prolonged window (12-h eating window/12-h fasting window) in adolescents with obesity (ages 14 to19, 72% female, 74% Hispanic). All youth completed the Pittsburgh Sleep Quality Index (PSQI) at baseline (n = 42), weeks 4 (n = 43), and 12 (n = 42). The seven component PSQI score, develops a global score that ranges from 0 to 21, where higher scores indicates worse sleep. Glycemic profiles were captured via continuous glucose monitors (CGM) worn for the duration of the study. Mixed effects generalized linear model in log scale and ordinal logistic regression models were utilized to (a) examine the change in PSQI total score and (b) assess the association between glycemic variability and PSQI total score overtime by intervention arm. Results Across all youth included in this analysis (n = 43), there was improvement in PSQI total score at week 12 compared to baseline that was marginally significant after adjusting for multiple testing (% change = -19.60, 95%CI = -31.83 to -5.18, p = 0.057). The median PSQI score for the TLE group (n = 29) was 6 at week 0 (5 to10) and 5 at week 12 (2.5 to 7), suggesting sleep quality improved. The changes in PSQI total score, sleep ratio, and sleep onset score over the course of study were not statistically different between groups (p > 0.05). There was no significant association between glycemic variability and PSQI score between the groups. Conclusion Findings from this secondary analysis indicate that TLE does not negatively alter sleep quality or duration in adolescents with obesity. The potential effects of TLE on sleep should be further investigated in larger randomized trials. Support (if any)

699-P: Time-Restricted Eating Did Not Alter Glycemic Variability in Humans Who Are Overweight and without Diabetes

Background: Time-restricted eating (TRE) is increasingly popular for weight loss, yet its effects on glycemic measures remain unclear. Using continuous glucose monitor (CGM) worn for 2 weeks at baseline and end-intervention, we hypothesized that TRE may reduce glycemic variability compared to unrestricted eating (non-TRE) in patients who are overweight and without diabetes. Method: Participants (17 women and 3 men; mean [SD] age: 45.5 [12.1] years; BMI 34.1 [7.5] kg/m2) without self-reported diabetes (HbA1c 5.5 [0.4]) who had prolonged eating window (15.4 [0.9] hours) were randomized to a 12 week intervention of either TRE (n=11: 8-hour window, unrestricted eating within window) versus non-TRE (n=9: unrestricted eating) . Each participant wore a blinded CGM (Freestyle Libre Pro) for 2 weeks prior to randomization and at end-intervention (week 11-12) . At each time point, multiple measures of glycemic variability were calculated from the raw CGM data. This is a secondary analysis of a previously published study where 12 weeks of TRE did not alter HbA1c. Result: Between the TRE and non-TRE groups in the pre and end-intervention periods, there was no statistical difference in any of the calculated glycemic variability measures: including, time in range (TIR) , standard deviation (SD) , coefficient of variation (CV) , continuous overlapping net glycemic action (CONGA) , liability, Index, J-index, low and high blood glucose index (LBGI/HBGI) , glycemic risk assessment diabetes equation (GRADE) , mean of daily differences (MODD) , average daily risk range (ADRR) , mean amplitude of glycemic excursions (MAGE) , mean of daily differences (MODD) , Area Under Curve (AUC) , and Glucose Management Indicator (GMI) . Conclusion: In patients who are overweight without diabetes, TRE did not alter CGM-measured glycemic variability. Further studies regarding TRE effects on glycemic variability should focus on participants with diabetes. Disclosure A.Mehfooz: None. Y.Lee: None. Q.Wang: None. L.S.Chow: Other Relationship; Dexcom, Inc.

Rest-activity profiles among U.S. adults in a nationally representative sample: a functional principal component analysis

BackgroundThe 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status.MethodsThe current analysis used data from adults 25 or older in the National Health and Nutrition Examination Survey (NHANES, 2011–2014). Using 7-day 24-h actigraphy recordings, we applied fPCA to derive profiles for overall, weekday and weekend rest-activity patterns. We examined the association between each rest-activity profile in relation to age, gender, race/ethnicity, education, income and working status using multiple linear regression. We also used multiple logistic regression to determine the relationship between each rest-activity profile and the likelihood of reporting poor or fair health.ResultsWe identified four distinct profiles (i.e., high amplitude, early rise, prolonged activity window, biphasic pattern) that together accounted for 86.8% of total variation in the study sample. We identified numerous associations between each rest-activity profile and multiple sociodemographic characteristics. We also found evidence suggesting the associations differed between weekdays and weekends. Finally, we reported that the rest-activity profiles were associated with self-rated health.ConclusionsOur study provided evidence suggesting that rest-activity patterns in human populations are shaped by multiple demographic, socioeconomic and work factors, and are correlated with health status.

Quasi-continuous production of highly hyperpolarized carbon-13 contrast agents every 15 seconds within an MRI system

Hyperpolarized contrast agents (HyCAs) have enabled unprecedented magnetic resonance imaging (MRI) of metabolism and pH in vivo. Producing HyCAs with currently available methods, however, is typically time and cost intensive. Here, we show virtually-continuous production of HyCAs using parahydrogen-induced polarization (PHIP), without stand-alone polarizer, but using a system integrated in an MRI instead. Polarization of ≈2% for [1-13C]succinate-d2 or ≈19% for hydroxyethyl-[1-13C]propionate-d3 was created every 15 s, for which fast, effective, and well-synchronized cycling of chemicals and reactions in conjunction with efficient spin-order transfer was key. We addressed these challenges using a dedicated, high-pressure, high-temperature reactor with integrated water-based heating and a setup operated via the MRI pulse program. As PHIP of several biologically relevant HyCAs has recently been described, this Rapid-PHIP technique promises fast preclinical studies, repeated administration or continuous infusion within a single lifetime of the agent, as well as a prolonged window for observation with signal averaging and dynamic monitoring of metabolic alterations.

Sex differences in alcohol dehydrogenase levels (ADH) and blood ethanol concentration (BEC) in Japanese quail

Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. In the bloodstream, ethanol is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). In mammals, females appear to have higher ADH activity in liver samples than males. The purpose of the first experiment was to analyze sex differences in ADH levels following 12 d of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized, their livers were extracted, and ADH was analyzed in liver homogenate samples. Results showed that female quail had higher ADH levels, heavier livers, and a greater liver to body weight ratio than male quail. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg of ethanol and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 h after gavage administration. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak of ethanol concentration and a smaller area under the curve (AUC) than male quail. The current research suggests that higher ADH levels in female quail may be responsible for increased metabolism of ethanol. In general, quail appear to eliminate ethanol more slowly than rodents. Thus, as a model, they may allow for a prolonged window with which to investigate the effects of ethanol.

Working through the fog of a pandemic: Street-level policy entrepreneurship in times of crises.

Imposing significant challenges for both street‐level implementation and policy (re)design, crises alter the environment for street‐level policy entrepreneurship (SLPE), wherein street‐level bureaucrats engage in policy formulation processes to secure future policy outcomes. Nevertheless, like street‐level implementation in general, SLPE is studied during ordinary times but rarely during crises. Focusing on community‐health workers in Brazil during the Covid‐19 crisis uncovered a defensive motivation for SLPE, which aimed to legitimize community healthcare as an integral part of pandemic treatment, reforming the government's hitherto neglectful approach to community health services. Moreover, the continuing crisis created an unusually prolonged window of opportunity for securing community healthcare provision. By utilizing collective efforts and drawing on powerful politicians' mobilization, SLPE during crisis shares similarities with, yet differs from, SLPE during ordinary times, while further closing the interstices between local, professional, and political perspectives in the formulation of policy decisions.

Scrambling and Lyapunov exponent in spatially extended systems

Scrambling of information in a quantum many-body system, quantified by the out-of-time-ordered correlator (OTOC), is a key manifestation of quantum chaos. A regime of exponential growth in the OTOC, characterized by a Lyapunov exponent, has so far mostly been observed in systems with a high-dimensional local Hilbert space and in weakly-coupled systems. Here, we propose a general criterion for the existence of a well-defined regime of exponential growth of the OTOC in spatially extended systems with local interactions. In such systems, we show that a parametrically long period of exponential growth requires the butterfly velocity to be much larger than the Lyapunov exponent times a microscopic length scale, such as the lattice spacing. As an explicit example, we study a random unitary circuit with tunable interactions. In this model, we show that in the weakly interacting limit the above criterion is satisfied, and there is a prolonged window of exponential growth. Our results are based on numerical simulations of both Clifford and universal random circuits supported by an analytical treatment.

2076-P: Time Restricted Eating (TRE) Promotes Weight Loss, Alters Body Composition, and Improves Metabolic Parameters in Overweight Humans

TRE, restriction of the eating window, reduces weight in animals and humans. We performed a randomized clinical trial examining the effect of TRE on body composition and glycemic measures in overweight humans without diabetes. We hypothesized that TRE will reduce weight and alter body composition compared with unrestricted feeding (non-TRE). 21 overweight subjects [18F/3M, mean(SE), age: 44.7 years (2.7), BMI:34.6 kg/m2(1.7) with a prolonged eating window:15.6 hours (0.2)] were randomized to either 12 weeks of TRE [n=11 (goal 8 hours)] or non-TRE [n=10]. All oral intake was logged using the myCircadianClock smart phone application to remotely monitor TRE adherence. Subjects also underwent: 2-hour oral glucose tolerance test, 2-week continuous glucose monitoring (Freestyle Libre), and 2-week activity tracking (Actigraph Link) pre and post intervention. Compared with the non-TRE group [eating window 15.2 hours (0.3)] post-intervention, the TRE group [eating window 10.4 hours (0.6)] decreased weight [-3.6 kg(0.6) vs. -1.4 kg(0.7)], visceral fat [-260 g(110) vs. 38 g(56)], lean mass [-1450 g(389) vs. -95.5 g(351)] and triglycerides [-23.6%(6.8) vs. -0.57%(7.6)] (all p≤0.05). Relative to baseline, the TRE group decreased: weight, fasting glucose, fat mass, lean mass, visceral fat, and fasting triglyceride levels (all p<0.05). This was not observed in the non-TRE group. TRE-related weight loss was associated with lower: fat mass [-4%(0.9)], visceral fat [-11%(4.0)], and lean mass [-3%(0.8)] relative to baseline (all p<0.05). All TRE-related effects were not significant after adjusting for weight loss. Neither intervention significantly altered physical activity. In overweight subjects, TRE reduced weight and improved metabolic parameters (triglycerides, fasting glucose). However, the TRE-related weight loss included both lean and fat mass loss. Further investigation into the translational aspects of TRE to treat obesity-related disorders is warranted. Disclosure L.S. Chow: Research Support; Self; Eli Lilly and Company. E. Manoogian: None. A.C. Alvear: None. Q. Wang: None. S. Panda: Other Relationship; Self; PenguinRandomHouse. D.G. Mashek: Consultant; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company. Funding University of Minnesota Healthy Foods Healthy Lives (17SFR-2YR50LC)

Abstract TMP33: Modulation of Receptor Protein Tyrosine Phosphatase Sigma Promotes Neuroregeneration and Functional Recovery After Ischemic Stroke

Introduction: Due to the limitation in current treatment window for stroke, the development of delayed stroke treatment is needed. The two main cellular processes of neural repair after stroke are axonal sprouting and neurogenesis. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are increased within the glial scar and perineuronal net after ischemic brain injury, which might play a critical role in blocking neuroblasts migration, axonal regrowth and sprouting. Recently, a novel small peptide memetic of the CSPG receptor (PTP σ) wedge region named ISP (Intracellular Sigma Peptide) is generated and has capabilities to target PTP σ and relieve CSPGs inhibition in the models of spinal cord injury. Here, we aimed to determine whether post-stroke ISP treatment could improve functional recovery in a mouse model of ischemia. Methods: Mice were subjected to tMCAO followed by treatment of ISP or vehicle daily for 4 weeks beginning 24h or 7 days post-tMCAO. Motor and sensorimotor functions were measured prior to MCAO and at 1, 2, 3 and 4 weeks post-stroke using locomotion analysis and adhesion removal test. Cognitive function was also assessed with Barnes maze test at 4 weeks post-stroke. Neurogenesis and axonal sprouting was evaluated using genetic labeling and immunohistochemical analysis. Results: Our results show that continuous ISP treatment starting at 24 hours post stroke improves both survival and long-term functional recovery after stroke and 7 day post-stroke treatment improves the functional recovery. Correlated with the improved behavior measurements, immunohistochemical analysis revealed that post-stroke ISP treatment increased the total number of newly generated neuroblast cells migrating towards the peri-infarct area as well as a robust sprouting/regeneration of serotonergic axons around the stroke peri-infarct area. Conclusions: Our data suggest that inhibition of PTP σ/CSPGs signaling by ISP stimulates functional recovery after stroke via promoting neuroblast migration and axonal growth. Pharmacological targeting of the PTP σ/CSPGs interaction is therefore a potential novel therapeutic strategy for stroke treatment, which may provide a prolonged treatment window for improving functional recovery after stroke.

Inflammatory Resolution Triggers Mononuclear Phagocyte Infiltration, Which through COX-1/mPGES-1 Maintains Immune Tolerance

While resolution is believed to switch inflammation off and return the affected tissues back to homeostasis, we found that it triggers a prolonged phase of immune suppression. During resolution of acute inflammation (∼72h) CD4+ and CD8+ lymphocytes as well as natural killer (NK) cells migrated into tissues secreting IFNγ from day 6. IFNγ carried out two distinct functions: firstly, through IP-10, IFNγ indirectly triggered monocyte infiltration, which differentiated into macrophages (moMϕs). Secondly, moMϕs were directly acted upon by IFNγ to express microsomal prostaglandin E synthase-1 (mPGES-1) alongside cyclooxygenase (COX 1) resulting in sustained prostaglandin (PG)E2 synthesis peaking at day 14 and lasting for several weeks. PGE2 suppressed innate immune responses to bacterial infection opening a prolonged window of postresolution infectious opportunity within the host. At the same time, it also differentially modulated multiple aspect of the adaptive immune system including suppressing lymphocyte function whilst also generating myeloid-derived suppressor cells, the net effect of which was impaired uptake/presentation of exogenous antigens. Therefore, we have defined a novel sequence of post-resolution events starting with IFNγ and culminating in sustained PGE2, which we propose dampens the propensity to develop autoimmune responses to endogenous antigens at the cost of local tissue infection.

Abstract 60: Sequential Combined Treatment of Pifithrin-a and (+)-phenserine Enhances Neurogenesis and Functional Recovery After Stroke

Background and Purpose: Due to the limitation in treatment window of the rtPA (recombinant tissue plasminogen activator), the development of delayed treatment for stroke is needed. Utilizing a specific p53 inhibitor (PFT-a), our group has previously reported enhanced proliferation and survival of endogenous progenitor cells in-vivo, leading to enhanced functional recovery in stroke animals days and weeks after stroke onset. Recently, a role for amyloid-ß protein precursor (APP) has been implicated in synapse formation, neural plasticity, and the differentiation of neural stem cells. In this study, we examined the efficacy of delayed post-stroke treatment of sequentially combined PFT-a (post-stroke day 5-12) and an amyloid precursor protein inhibitor, (+)-phenserine (post stroke day 13-27) on functional recovery after stroke and the response of endogenous neural progenitor cells in SVZ and SGZ in stroke animals. Methods: We utilized a genetically inducible NSC-specific reporter mouse line (nestin-CreERT2-R26R-YFP) to label and track neural stem cell proliferation, survival, and differentiation in ischemic brain. We evaluated functional recovery at 4 weeks after stroke using locomotion analysis, novel object recognition and Barnes maze tests for cognitive function. Results: Our results show that delayed and combined treatment with PFT-a and (+)-phenserine resulted in increased proliferation and differentiation of YFP positive neuronal stem cells in post-stroke mice compared to vehicle treated stroke mice. In addition, the combined treatment cohort showed improved functional recovery in both locomotor (open field) and cognitive functions (NOR and Barnes maze) starting at 2 weeks post stroke and sustained up to 4 weeks after stroke. Conclusions: Our data suggest that sequential combination treatment strategy that enhances proliferation and neuronal differentiation of endogenous neural stem cells can work synergistically and improve the functional recovery after stroke through increased neurogenesis. This may provide a prolonged treatment window for improving functional recovery after stroke.

Temporal processing deficit leads to impaired multisensory binding in schizophrenia

ABSTRACTIntroduction: Schizophrenia has been characterised by neurodevelopmental dysconnectivity resulting in cognitive and perceptual dysmetria. Hence patients with schizophrenia may be impaired to detect the temporal relationship between stimuli in different sensory modalities. However, only a few studies described deficit in perception of temporally asynchronous multisensory stimuli in schizophrenia.Methods: We examined the perceptual bias and the processing time of synchronous and delayed sounds in the streaming–bouncing illusion in 16 patients with schizophrenia and a matched control group of 18 participants.Results: Equal for patients and controls, the synchronous sound biased the percept of two moving squares towards bouncing as opposed to the more frequent streaming percept in the condition without sound. In healthy controls, a delay of the sound presentation significantly reduced the bias and led to prolonged processing time whereas patients with schizophrenia did not differentiate between this condition and the condition with synchronous sound.Conclusion: Schizophrenia leads to a prolonged window of simultaneity for audiovisual stimuli. Therefore, temporal processing deficit in schizophrenia can lead to hyperintegration of temporally unmatched multisensory stimuli.

Slow-growth high-mortality: A meta-analysis for insects.

The slow growth-high mortality hypothesis (SG-HG) predicts that slower growing herbivores suffer greater mortality due to a prolonged window of vulnerability. Given diverse plant-herbivore-natural enemy systems resulting from different feeding ecologies of herbivores and natural enemies, this hypothesis might not always be applicable to all systems. This is evidenced by mixed support from empirical data. In this study, a meta-analysis of the SG-HM hypothesis for insects was conducted, aiming to find conditions that favor or reject SG-HM. The analysis revealed significant within- and between-group heterogeneity for almost all explanatory variables and overall did not support SG-HM. In this analysis, SG-HM was supported when any of the following 5 conditions was met: (1) host food consisted of artificial diet; (2) herbivore growth was measured as larval mass; (3) herbivores were generalists; (4) no or multiple species of natural enemies were involved in the study; and (5) parasitoids (i.e., parasitic insects) involved in the study were gregarious. SG-HM was rejected when any of the following 5 conditions was met: (1) herbivores were from the order Hymentoptera; (2) parasitoids from more than 1 order caused herbivore mortality; (2) parasitoids were specialists; (3) parasitoids were solitary; (4) parasitoids were idiobionts or koinobionts; and (5) single species of natural enemy caused mortality of specialist herbivores. All known studies investigated herbivore mortality for a short period of their life cycle. Researchers are encouraged to monitor herbivore mortality during the entire window of susceptibility or life cycle using life tables. Studies involving multiple mortality factors (i.e., both biotic and abiotic) or multiple natural enemy species are also encouraged since herbivores in nature face a multitude of risks during the entire life cycle. More comprehensive studies may increase our understanding of factors influencing the relationships between herbivore growth and mortality.

Severe stress hormone conditions cause an extended window of excitability in the mouse basolateral amygdala

Shortly after stress, basolateral amygdala neurons are exposed to sequential yet partly overlapping waves of hormones. We examined how these hormonal waves can change activity of basolateral amygdala neurons such that emotional aspects of stress become so deeply ingrained. To this end, spontaneous glutamatergic transmission was recorded during and up to several hours after combined adrenergic and corticosteroid waves, targeting the time-window relevant for encoding of stress-related information. Hormonal waves mimicking moderately stressful conditions cause a transient enhancement followed by later suppression of glutamatergic transmission. However, this late phase flips from suppressed to enhanced glutamatergic transmission with conditions mimicking severe stress. Such a prolonged window of enhanced excitability may contribute to the excessively strong encoding seen after the experience of highly stressful or traumatic events.

Does the occupant behavior match the energy concept of the building? – Analysis of a German naturally ventilated office building

Experiences show that there is often a large gap between the predicted energy demand and the consumption once the building is in use. One cause could be that the occupant behavior might not fit with the energy concept and cause counterproductive behavior. This paper is based on simple statistics as well as logistic regression analyses in order to evaluate how much the occupants interact with their building in a manner suitable to the building concept with natural ventilation. As case study, monitoring data from an office building in Frankfurt, Germany, is taken. The findings show that behavior profiles of window opening give helpful hints regarding the interaction between building and occupants. The window opening times in winter are in 10–25% of the days too long. The window opening in summer are in 10–40% of the times not supporting the building concept due to windows being opened while the outdoor temperature is higher than the indoor air temperature. These non optimal behaviors could be linked directly (by experts and occupants) to an increased energy consumption in winter. In the summer case, prolonged window opening at high outdoor temperatures does not lead directly to a higher energy demand, because no cooling system exists. However, the increased heat gain leads to a higher demand for night ventilation, which in some cases is facilitated by an electrical fan. In such a way, the auxiliary energy demand can be increased.

Abstract 3975: Regression of established tumors requires timely adoptive T cell transfer following whole body irradiation.

Abstract Adoptive immunotherapy with CD8+ T cells has achieved some success in treating established cancer. Response rates are increased by preconditioning the patient with lymphodepleting whole body irradiation (WBI) prior to T cell transfer, including an increased fraction of complete responses. Using a mouse model of autochthonous brain cancer, we previously demonstrated that adoptive transfer of tumor-specific T cells following WBI promotes complete regression of established tumors and long-term survival. However, the mechanisms required to achieve complete responses remain to be defined. Here we investigate kinetic requirements for adoptive T cell transfer to achieve tumor control following WBI. To test the hypothesis that adoptive transfer early after irradiation is required for maximum long-term tumor control, we delayed adoptive transfer of T cells to tumor-bearing mice at varying intervals following irradiation. We show that delay of adoptive transfer did not affect initial T cell priming or the timing of initial appearance of activated T cells at the tumor site. However, we observed a modest decrease in T cell accumulation at the earliest appearance of cells in the brain (5 days post-transfer). Tumors were completely eliminated within 10 days in mice that received T cell transfer one day following WBI, while delayed transfer abrogated this effect. When adoptive transfer was delayed by one week following WBI, incomplete tumor regression was observed at 10 days post-transfer. Although mice in this group lived significantly longer than control animals, they eventually succumbed to lethal tumor recurrence. Our data suggest that lymphodepleting doses of WBI promote a prolonged window for effective T cell priming against the endogenous tumor antigen, but that optimal therapeutic potential requires T cell transfer early after irradiation conditioning. Supported by research grant CA02500 from the National Cancer Institute/National Institutes of Health. Citation Format: Eugene M. Cozza, Lynn R. Budgeon, Neil D. Christensen, Todd D. Schell. Regression of established tumors requires timely adoptive T cell transfer following whole body irradiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3975. doi:10.1158/1538-7445.AM2013-3975

Long-Term Stimulation of Neural Progenitor Cell Migration After Cortical Ischemia in Mice

Cortical ischemia induces neural progenitor cell migration toward the injury site; however, whether these cells are capable of maintaining the migratory response for a longer period after injury remains uncertain. We analyzed progenitor migration up to 1 year after induction of photothrombotic stroke to the mouse neocortex. Migrating progenitors identified as doublecortin positive cells (DCX+) were assessed using the immunohistochemistry and immunofluorescence. The thymidine analogues chlorodeoxyuridine and iododeoxyuridine were used to birth-date the progenitor cells. In the striatum, we detected elevated numbers of DCX+ cells up to 6 weeks postlesion. In the corpus callosum and the peri-infarct cortex (Ctx), DCX+ cell numbers were increased up to 1 year. The orientation of the migrating progenitors was mostly aligned with the corpus callosum fiber tract at all time points; however, in the Ctx, they aligned parallel to the infarct border. The injured cortex continuously receives new progenitors up to 1 year after lesion. Cells born after lesion did not become mature neurons, although a portion of the migrating progenitors showed initial signs of differentiation into neurons. Neural progenitors might have a role in brain plasticity after cortical stroke, especially considering the prolonged window of migratory responses of up to 1 year after stroke lesion.

Brain function during probabilistic learning in relation to IQ and level of education

Knowing how to adapt your behavior based on feedback lies at the core of successful learning. We investigated the relation between brain function, grey matter volume, educational level and IQ in a Dutch adolescent sample. In total 45 healthy volunteers between ages 13 and 16 were recruited from schools for pre-vocational and pre-university education. For each individual, IQ was estimated using two subtests from the WISC-III-R (similarities and block design). While in the magnetic resonance imaging (MRI) scanner, participants performed a probabilistic learning task. Behavioral comparisons showed that participants with higher IQ used a more adaptive learning strategy after receiving positive feedback. Analysis of neural activation revealed that higher IQ was associated with increased activation in DLPFC and dACC when receiving positive feedback, specifically for rules with low reward probability (i.e., unexpected positive feedback). Furthermore, VBM analyses revealed that IQ correlated positively with grey matter volume within these regions. These results provide support for IQ-related individual differences in the developmental time courses of neural circuitry supporting feedback-based learning. Current findings are interpreted in terms of a prolonged window of flexibility and opportunity for adolescents with higher IQ scores.