The quantum maxima for the basic graphs of exclusivity are not reachable in Bell scenarios.

A necessary condition for the probabilities of a set of events to exhibit Bell non-locality or Kochen-Specker contextuality is that the graph of exclusivity of the events contains induced odd cycles with five or more vertices, called odd holes, or their complements, called odd antiholes. From this perspective, events whose graph of exclusivity are odd holes or antiholes are the building blocks of contextuality. For any odd hole or antihole, any assignment of probabilities allowed by quantum theory can be achieved in specific contextuality scenarios. However, here we prove that, for any odd hole, the probabilities that attain the quantum maxima cannot be achieved in Bell scenarios. We also prove it for the simplest odd antiholes. This leads us to the conjecture that the quantum maxima for any of the building blocks cannot be achieved in Bell scenarios. This result sheds light on why the problem of whether a probability assignment is quantum is decidable, while whether a probability assignment within a given Bell scenario is quantum is, in general, undecidable. This also helps to understand why identifying principles for quantum correlations is simpler when we start by identifying principles for quantum sets of probabilities defined with no reference to specific scenarios. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

Effects of dried plum supplementation on bone metabolism in adult C57BL/6 male mice.

Dietary supplementation of dried plum (DP) prevents bone loss and restores bone mass in osteopenic animal models. This study was designed to determine the effects of DP supplementation on bone metabolic activity over time using adult (6-month-old) male C57BL/6 mice (n = 40) receiving control (CON = AIN93 M) or CON+DP 25 % (w/w) diets for 4 or 12 weeks. After 4 weeks of treatment, animals consuming the DP diet had a higher whole-body bone mineral density, vertebral trabecular bone volume (BV/TV), and femoral cortical thickness compared to the CON animals. In the distal metaphysis of the femur, BV/TV was increased in the DP-treated animals, but only after 12 weeks. Bone histomorphometric analyses revealed that DP decreased osteoblast surface (67 %) and osteoclast surface (62 %) at 4 weeks, but these surfaces normalized to the CON animals by 12 weeks. Coincident with these changes, the mineralizing surface (MS/BS) and cancellous bone formation rate (BFR/BS) were reduced at 4 weeks in the DP group compared to the CON, but by 12 weeks of DP supplementation, BFR/BS (~twofold) and MS/BS (~1.7-fold) tended to be increased (p < 0.10). The relative abundance of RNA for key regulators of osteoblast and osteoclast differentiation and indicators of osteoblast activity were reduced in the DP group at 4 weeks with no difference between groups at 12 weeks. These results indicate that supplementing the diet with DP initially suppressed cancellous bone turnover, but a biphasic response occurs over time, resulting in a positive effect on bone mass and structure.

Operating semiconductor quantum processors with hopping spins.

Qubits that can be efficiently controlled are essential for the development of scalable quantum hardware. Although resonant control is used to execute high-fidelity quantum gates, the scalability is challenged by the integration of high-frequency oscillating signals, qubit cross-talk, and heating. Here, we show that by engineering the hopping of spins between quantum dots with a site-dependent spin quantization axis, quantum control can be established with discrete signals. We demonstrate hopping-based quantum logic and obtain single-qubit gate fidelities of 99.97%, coherent shuttling fidelities of 99.992% per hop, and a two-qubit gate fidelity of 99.3%, corresponding to error rates that have been predicted to allow for quantum error correction. We also show that hopping spins constitute a tuning method by statistically mapping the coherence of a 10-quantum dot system. Our results show that dense quantum dot arrays with sparse occupation could be developed for efficient and high-connectivity qubit registers.

Atomic fluctuations lifting the energy degeneracy in Si/SiGe quantum dots.

Electron spins in Si/SiGe quantum wells suffer from nearly degenerate conduction band valleys, which compete with the spin degree of freedom in the formation of qubits. Despite attempts to enhance the valley energy splitting deterministically, by engineering a sharp interface, valley splitting fluctuations remain a serious problem for qubit uniformity, needed to scale up to large quantum processors. Here, we elucidate and statistically predict the valley splitting by the holistic integration of 3D atomic-level properties, theory and transport. We find that the concentration fluctuations of Si and Ge atoms within the 3D landscape of Si/SiGe interfaces can explain the observed large spread of valley splitting from measurements on many quantum dot devices. Against the prevailing belief, we propose to boost these random alloy composition fluctuations by incorporating Ge atoms in the Si quantum well to statistically enhance valley splitting.

Supreme Court v. Necropolitics: The Chaotic Judicialization of COVID-19 in Brazil.

Worldwide, governments have reacted to the COVID-19 pandemic with emergency orders and policies restricting rights to movement, assembly, and education that have impacted daily lives and livelihoods in profound ways. But some leaders, such as President Jair Bolsonaro in Brazil, have resisted taking such steps, denying the seriousness of the pandemic and sabotaging local control measures, thereby compromising population health. Facing one of the world's highest rates of COVID-19 infections and deaths, multiple political actors in Brazil have resorted to judicialization to advance the right to health and other protections in the country. Responding to this litigation has provided the country's Supreme Court an opportunity to assertively confront and counter the executive's necropolitics. In this article, we probe the malleable form and the constitutional basis of the Supreme Court's decisions, assessing their impact on the separation of powers, on the protection of human rights (for example, on those of prisoners, indigenous peoples, and essential workers), and relative to the implementation of evidence-based interventions (for example, lockdowns and vaccination). While the court's actions open up a distinct legal-political field (sometimes called "supremocracy")-oscillating between progressive imperatives, neoliberal valuations, and conservative decisions-the capacity of the judiciary to significantly address systemic violence and to robustly advance human rights remains to be seen.

Systemic bone loss and induction of coronary vessel disease in a rat model of chronic inflammation.

Clinically, osteopenia or low bone mass has been observed in a variety of chronic inflammatory diseases, and elevated proinflammatory mediators have implicated this process. The purpose of this study was to develop an in vivo model of bone loss induced by chronic systemic inflammation. Time-release pellets designed to deliver one of three doses of LPS: Low (3.3 microg/day), High (33.3 microg/day), or Placebo over 90 days, were implanted subcutaneously in 3-month-old male Sprague-Dawley rats (n = 8/group). Neutrophil counts, indicative of ongoing inflammation, were elevated (P < 0.05) in both LPS groups at 30 days post-implant and remained significantly elevated in the High dose throughout the 90-day study period. At the end of the study, bone loss occurred in the femur as indicated by decreased bone mineral density (BMD) in both LPS-treated groups, but vertebral BMD was reduced in the High dose animals only. Microcomputed tomography revealed that trabecular bone volume (BV/TV) of the proximal tibial metaphysis tended to be reduced in the High dose LPS group. Deleterious effects on trabecular number (TbN) and trabecular separation (TbSp) were observed in both LPS-treated groups, but only the High dose group reached statistical significance. These alterations in trabecular microarchitecture resulted in compromised biomechanical properties. No changes in cortical thickness, porosity, or area of the tibia midshaft were evident at either dose of LPS. Up-regulation of the proinflammatory mediators, cyclooxygenase (COX)-2, interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha was demonstrated in the metaphyseal region where the deleterious effects of LPS were observed. In addition to these alterations in bone, trichrome staining indicated changes in the coronary arterioles, consistent with vascular disease. Utilization of a LPS time-release pellet appears to provide an in vivo model of chronic inflammation-induced bone loss and a potentially novel system to study concurrent development of osteopenia and vascular disease.

Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway.

Previously, dietary supplementation with dried plums, a rich source of polyphenolic compounds with antioxidant and anti-inflammatory properties, has been shown to improve bone density, microstructure and biomechanics in female animal models of osteopenia. We designed this study to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand its mechanism of action. Sixty 6-month-old male Sprague-Dawley rats were either sham-operated (Sham = 1 group) or orchidectomized (ORX = 4 groups) and randomly assigned to dietary treatments: standard semi-purified diet (Control) with either LD = 5%, MD = 15%, or HD = 25% (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and HD dried plum completely prevented the ORX-induced decrease in whole body, femur, and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate load of the cortical bone as well as the compressive force and stiffness of trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of the distal femur metaphysis and vertebral body revealed that HD dried plum protected against the decrease in trabecular bone volume (BV/TV) induced by ORX. In the distal femur, all doses of dried plum improved trabecular number (TbN) and separation (TbSp) compared to the ORX-control group, while MD and HD dried plum prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90-day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase in any of the treatment groups were observed, while serum insulin-like growth factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFkappa-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that dried plum prevents osteopenia in androgen deficient male rats, and these beneficial effects may be attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.

Impaired glucose tolerance attenuates bone accrual by promoting the maturation of osteoblasts: Role of Beclin1-mediated autophagy.

Patients with type 2 diabetes mellitus (T2DM) experience a 1.5-3.5 fold increase in fracture risk, but the mechanisms responsible for these alterations in bone biomechanical properties remain elusive. Macroautophagy, often referred to as autophagy, is regulated by signaling downstream of the insulin receptor. Metabolic changes associated with the progression of glucose intolerance have been shown to alter autophagy in various tissues, but limited information is available in relation to bone cells. The aim of this study was to (a) investigate whether autophagy is altered in bone tissue during impaired glucose tolerance, and (b) determine how autophagy impacts osteoblast differentiation, activity, and maturation. Four-week-old, male C57BL/6 mice were fed a control (Con) or high fat (HF) diet for 2, 8, or 16 wks. Mice on the HF diet demonstrated elevated fasting blood glucose and impaired glucose tolerance. Reduced trabecular bone in the femoral neck was evident in the mice on the HF diet by 8 wks compared to Con mice. Histological evaluation of the tibia suggested that the high fat diet promoted terminal differentiation of the osteoblast to an osteocyte. This shift of the osteoblasts towards a non-mineralizing, osteocyte phenotype appears to be coordinated by Beclin1-mediated autophagy. Consistent with these changes in the osteoblast in vivo, the induction of autophagy was able to direct MC3T3-E1 cells towards a more mature osteoblast phenotype. Although these data are somewhat observational, further investigation is warranted to determine if Beclin1-mediated autophagy is essential for the terminal differentiation of the osteoblasts and whether autophagy is having a protective or deleterious effect on bone in T2DM.

Effects of a short light-dark cycle on the sleep-wake patterns of the cat.

The purpose of this study was to measure the effect of a short, 106 min, light-dark (LD) cycle on the sleep-wake (SW) patterns of the cat. Eight cats prepared for chronic sleep studies were observed with electrographic tracings for 48 hr on a regular 12:12 hr LD schedule and again after 2 weeks of adaptation to a 27 min light and 79 min dark schedule. Each 1 min of data was scored as either alert, drowsy, slow wave sleep (SWS) or REM sleep. The parameters studied were percent electrographic state, state epoch length, polycyclic SW cycle, and mean vigilance. The short LD cycle caused a significant increase in alert state accompanied by reductions in drowsy, SWS, and REM sleep states. Although the effect was more pronounced during lights-on intervals, the trend was also present in dark intervals. Alert episodes of about all lengths increased. There were decreases in longer episodes of the other three states and a tendency for shorter episodes to increase in number. Episodes of the polycyclic SW cycle did not tend to follow the short LD cycle. The mean length of both sleep and wake episodes increased rather than decreased. However, mean vigilance values increased toward wakefulness at or near the light interval. Analyses showed that both the amplitude and phase relationship of this increase was significantly related to the 27 min light interval in comparison to base-line data. It was hypothesized that both light-dark and dark-light transitions represent alerting cues to the cat. Differences between the SW response of the cat and the rat to LD cycles are discussed.

A sleep laboratory evaluation of an automatic positive airway pressure system for treatment of obstructive sleep apnea.

STUDY OBJECTIVES: This paper compares the performance of an experimental nasal positive airway pressure device that automatically adjusts the level of applied pressure (APAP) with the performance of a conventional continuous positive airway pressure (CPAP) in a sleep laboratory study. DESIGN: In a randomized sequence, conventional CPAP therapy was applied for 1 night (CPAP night) and APAP therapy the following night (APAP night). SETTING: The study was conducted in an accredited sleep disorders center. PATIENTS OR PARTICIPANTS: Twenty-six men and 5 women between the ages of 35 to 73 (51 +/- 9.6) years with body mass index 35.82 +/- 8.35 (kg/m2) who were diagnosed (using standard nocturnal polysomnography [NPSG] methods) as having OSA syndrome were studied. The subjects were treated with conventional CPAP for approximately 8 (7.79 +/- 3.16) weeks at home prior to their participation in this study. MEASUREMENTS AND RESULTS: All standard polysomnography data and nasal mask pressures were recorded using a computer-based data acquisition system. Sleep and respiratory data were scored by a registered polysomnographer. The mean apnea-hypopnea index (AHI) for subjects for the NPSG night was 55.2 +/- 33.7. It dropped to 4.2 +/- 3.8 for the CPAP night and to 5.4 +/- 5.4 for the APAP night. There was no significant (p = 0.05) difference between mean AHI indices, sleep stages, sleep stage shifts, and snore arousals for CPAP night and APAP night. However, all the measures showed significant (p = 0.05) improvement over NPSG night. The mean of APAP applied pressure (8.4 +/- 3.3 cm H2O) was significantly (p = 0.05) lower than the prescribed pressure (11.5 +/- 3.1 cm H2O), but there was no significant (p = 0.05) difference between the maximum APAP applied pressure (12.8 +/- 4.3 cm H2O) and the prescribed pressure (11.5 +/- 3.1 cm H2O). All mean comparison tests were carried out using two-tailed statistics. CONCLUSIONS: APAP appears to be as effective as CPAP in treating OSA patients. APAP delivers the same level of therapy as CPAP, but it reduces the average airway pressure while providing needed peak pressures.

Effect of amphetamine and pentobarbital on sleep-wake patterns of cats with basal forebrain lesions.

The effects of amphetamine and pentobarbital upon electrographic state were studied in naive cats and cats with forebrain lesions that induce insomnia. Amphetamine increased alertness and decreased both slow wave sleep (SWS) and rapid eye movement (REM) sleep states for up to 12 h in both intact animals and cats with lesions. Pentobarbital inhibited REM sleep and alert states while increasing SWS and drowsy states in naive cats. The effect was mainly restricted to the first 8 h. In cats with forebrain lesions, the effects were similar except that the amount of REM sleep was significantly elevated. During a portion of the first 8 h, the tracing cannot be distinguished from a normal control sample. It is hypothesized that pentobarbital mimics the normal inhibitory influence of the intact forebrain and either induces or facilitates 'normal' sleep patterns in cats with forebrain lesions.

Prune suppresses ovariectomy-induced hypercholesterolemia in rats.

Elevated cholesterol among women who have experienced natural or surgical menopause has been linked to ovarian hormone deficiency. The purpose of this study was to investigate the efficacy of prune, a good source of dietary fiber and phytochemicals, on lowering cholesterol in an ovariectomized (ovx) rat model. Forty-eight 90-day-old female Sprague-Dawley rats were randomly assigned to four groups: sham-operated (sham) + control diet, ovx + control diet, ovx + low-dose (LD; 5%) prune, and ovx + high-dose (HD; 25%) prune. After 45 days of treatment, rats were euthanized and tissues were collected for analyses. Ovariectomy elevated serum total cholesterol by 22% compared with sham, and HD prune diet prevented this increase without affecting high density lipoprotein cholesterol concentrations. Animals fed the HD prune diet had 13% lower liver total lipids compared with ovx animals. The findings of this study showed that prune exhibits hypocholesterolemic properties in ovarian hormone deficiency. Dose-response studies should be conducted to establish the effectiveness of prune in prevention of hypercholesterolemia in postmenopausal women who are not on estrogen replacement therapy and seek dietary alternatives. Mechanistic studies also are needed to establish its mode of action.

Baseline sleep-wake patterns in the pointer dog.

The 24-hr electrographic patterns (EEG, EOG, EMG) of six normal pointer dogs were recorded in a laboratory setting. Two states of sleep (slow-wave and rapid eye movement) and wakefulness (alert and drowsy) were identified. The total recording period comprised 44% of alert wakefulness, 21% of the drowsy state, while slow-wave sleep occupied 23% and REM sleep 12% of the time. The mean length of a REM sleep episode averaged 6 min and the mean REM sleep cycle was 20 min. The mean polycyclic sleep-wake cycle was 83 min. Sleep episodes averaged 45 min and the mean waking episode was 38 min. There was an average of two REM sleep episodes per sleep-wake cycle. The dog has a propensity to sleep over a 16-hr interval from 1300 to 0500 but the most sleep occurred between 2100 and 0400 hr during darkness.

Determination of enantiomers in ephedrine mixtures by polarimetry.

Enantiomeric purities have been measured with precisions that are equivalent to those obtained from chiral chromatography by a simple ligand substitution reaction into the first coordination sphere of Cu(II)-tartrate complexes. The model systems are binary mixtures of the ephedrines. Ligand exchange reactions are done in bulk aqueous media. The detector is polarimetry. Multivariate regression analyses of optical rotation data measured at five wavelengths are used to prepare calibration and prediction models for binary mixtures of the enantiomers.

Automatic control of airway pressure for treatment of obstructive sleep apnea.

Obstructive sleep apnea (OSA) occurs when airflow ceases because of pharyngeal wall collapse in sleep. Repeated apneic events results in the development of a pathological condition called OSA syndrome. We describe the methodology and design of a prosthetic device, named automatic positive airway pressure (APAP), for treatment of this syndrome. APAP applies a stream of air via a nasal mask at an initial pressure selected by the patient. By sensing specific pressure characteristics of air flow immediately preceding pharyngeal wall collapse, the APAP device automatically raises the applied pressure to maintain a patent upper airway and thus prevent apnea. Conversely, when such conditions are absent, pressure is lowered step wise until a preselected minimum pressure is reached. Performance evaluation of the APAP system in five OSA patients and five normal (asymptomatic for sleep apnea) subjects revealed that it effectively treated OSA syndrome. It lowered the apnea-hypopnea index without disturbing sleep and resulted in a lower mean airway pressure compared to the traditional continuous positive airway pressure (CPAP) therapy. The results also show that the pressure needed to prevent OSA varied significantly throughout the night. For OSA syndrome patients, this pressure ranged from 3 to 18 cm H2O. The mean airway pressure for these patients had a sample average of 6.80 cm H2O and a standard deviation of 3.17 cm H2O. In normal subjects, the device did not raise pressure except in response to Pharyngeal Wall Vibration events.

A noninvasive technique for detecting obstructive and central sleep apnea.

A new noninvasive method to detect obstructive and central sleep apnea [(OSA) and (CSA)] events is described. Data were collected from ten volunteer subjects with a previous diagnosis of OSA while they were titrated for continuous positive airway pressure (CPAP) therapy. Apneic events were identify by analyzing of estimated airway impedance determined from pressure and airflow signals delivered from CPAP. To enhance performance of this technique, a single-frequency (5 Hz with 0.5 cmH2O peak-to-peak amplitude) probing signal was superimposed on the applied CPAP pressure. The results indicated that estimated airway impedance during OSA (mean: 17.9, SD: 3.4, N = 50) was significantly higher then during CSA (mean: 4.1, SD: 1.7, N = 50). When the estimated impedance of OSA and CSA events were compared to a fixed threshold, 100% of all events can be correctly categorized. These results indicate that it may be possible to diagnose OSA and CSA noninvasively based upon this technique. The instrument and the algorithm required are relatively simple and can be incorporated in a home-based device. If this method was used for prescreening apnea patients, it could reduce cost, waiting time, and discomfort associated with traditional diagnostic procedures.

Pharyngeal wall vibration detection using an artificial neural network.

An artificial-neural-network-based detector of pharyngeal wall vibration (PWV) is presented. PWV signals the imminent occurrence of obstructive sleep apnoea (OSA) in adults who suffer from OSA syndrome. Automated detection of PWV is very important in enhancing continuous positive airway pressure (CPAP) therapy by allowing automatic adjustment of the applied airway pressure by a procedure called automatic positive airway pressure (APAP) therapy. A network with 15 inputs, one output, and two hidden layers, each with two Adaline-nodes, is used as part of a PWV detection scheme. The network is initially trained using nasal mask pressure data from five positively diagnosed OSA patients. The performance of the ANN-based detector is evaluated using data from five different OSA patients. The results show that on the average it correctly detects the presence of PWV events at a rate of approximately 92% and correctly distinguishes normal breaths approximately 98% of the time. Further, the ANN-based detector accuracy is not affected by the pressure level required for therapy.

The energetic costs of diving in Aedes aegypti and Aedes albopictus pupae.

Undisturbed mosquito pupae rest at the water surface and respond to passing shadows or vibrations by diving. Pupae do not feed and rely solely on energy stored from the larval stage. The ability of a newly emerged adult mosquito to survive, and therefore to transmit disease, depends on these energy reserves. Earlier studies of diving behavior in Aedes aegypti, Ae. albopictus, and Ae. triseriatus pupae provided evidence that pupae sense their state of buoyancy and modify their diving behavior accordingly. With strong stimulation pupae tend to dive to a depth where they become neutrally or negatively buoyant and commonly rest on the bottom. This behavior, as well as the tendency to rest when not disturbed, may logically be viewed as energy-conserving. The results of these studies also generated the hypothesis that the diving behavior displayed by these container-breeding mosquitoes helps them avoid being washed from their container by overflowing water during rainfall. Rainfall stimulates diving and logically, prolonged, heavy rainfall stimulates excessive diving, a likely drain on energy reserves. Our objectives were to determine, in Ae. aegypti and Ae. albopictus, the energetic costs associated with resting behavior, with frequent diving, and with buoyancy reduction. Using survival rate, mean survival after adult emergence, and measurement of total calories, we found a clear energetic cost associated with frequent diving. In contrast, relative to diving, essentially no energy cost was associated with buoyancy reduction, that is, pupae behave in response to variations in buoyancy in a way that does not impact significantly on energy reserves.

Buoyancy and diving behavior in mosquito pupae.

Mosquito pupal diving behavior has been studied mostly in Aedes aegypti and in this species pupal buoyancy varies relative to several factors. The research reported herein addresses the 2 following questions. Does diving behavior vary among different mosquito genera and species? How is diving behavior influenced by variation in buoyancy? Depth and duration of dive, and dive pattern, were compared among Ae. aegypti, Culex pipiens, Anopheles stephensi, Aedes albopictus, and Aedes triseriatus. In response to the stimulation associated with transferring pupae between containers, diving behavior varied dramatically among the different genera studied. Culex pipiens and An. stephensi make short-duration, shallow dives and remain positively buoyant. The 3 aedine species studied make longer-duration dives, typically to a depth at which they become neutrally or negatively buoyant. Buoyancy reduction effects were studied in the 3 aedine species. Normally buoyant pupae tend to dive to greater depths and for longer periods of time than reduced-buoyancy pupae. Aedine pupal diving behavior clearly is closely regulated relative to buoyancy variation. To the earlier hypotheses that pupal behavior may help avoid predation and be energy-conserving, we add the suggestion that the diving behavior displayed by the container-breeding aedine pupae we studied represents an adaptation that helps keep them from being washed from their container habitat by overflowing water during rainfall. We also suggest that the diving behavior of all the species studied may help pupae survive heavy, pelting rainfall by enabling them to avoid the mechanical shock of a direct hit by a raindrop, which could cause disruption of the gas in the ventral air space, thereby causing the loss of hydrostatic balance and drowning.

Historical comments on chronobiology with emphasis on cell proliferation, the concept of free running, cancer chemotherapy and experimental design.

A brief historical summary is presented regarding the emergence, over the past several decades, of chronobiology as the newest of the integrating discipline of biology. The emphasis is on the circadian system which normally is synchronized to the 24 h environmental light-dark cycle. In the absence of a suitable synchronizer, the system free runs on its own endogenous genetically determined frequency, which usually only approximates 24 h. Since the metabolic system changes rhythmically in time it follows that an organism such as man is biochemically and physiologically a different entity at different circadian stages; therefore it reacts differently to an identical stimulus given at different times. Different stimuli such as anticancer agents are examples considered clearly timed treatment has been shown to significantly improve therapeutic efficacy, data will be presented using the L1210 mouse leukemic model. Moreover data is presented showing that to ignore such rhythmic fluctuation when designing experiments that such can bring about experimental error and false interpretation. The common "same time of day" sampling does not take care of the rhythmic problem!