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R J Nelson

Publications and source records attributed to R J Nelson.

At least 55 records · Page 3Linked to original sources

Experimental demonstration of fully coherent quantum feedback.

In the conventional picture of quantum feedback, control sensors make measurements on a quantum system, a classical controller processes the results of the measurements, and semiclassical actuators act back on the system to alter its behavior. We describe and provide an experimental demonstration of an alternative method for quantum feedback control, in which the sensors, controller, and actuators of conventional feedback control are replaced with quantum systems that interact coherently with the system to be controlled. The resulting control system represents a fully coherent quantum feedback loop.

Alanine↗

3-bromo-7-nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs maternal aggression and citrulline immunoreactivity in prairie voles.

Lactating female rodents are aggressive against intruders when they are rearing and protecting pups. In prairie voles, Microtus ochrogaster, females exhibit a dramatic increase in citrulline immunoreactivity (citrulline-IR) in the paraventricular nucleus (PVN), but not in control regions of the brain, in association with maternal aggression. Citrulline is an indirect indicator of nitric oxide (NO) synthesis and it is possible that NO release in the PVN is an important element in the control of maternal aggression in prairie voles. In this study, we sought to examine the role of NO in maternal aggression by selectively inhibiting neuronal nitric oxide synthase (nNOS) in lactating prairie voles. Intraperitoneal injections of the nNOS inhibitor, 3-bromo-7-nitroindazole (3-Br-7NI) (20 mg/kg), three time per day over 4 days resulted in significant impairment of the expression of maternal aggression in terms of the average time in aggressive encounters, the average number of attacks, and the average latency to first attack. These behavioral deficiencies were observable beginning two days following the onset of drug treatment. The average time spent sniffing the intruder was indistinguishable between the 3-Br-7NI- and oil-treated females. In 3-Br-7NI-treated relative to oil-treated females, the number of citrulline-positive cells was reduced by 70% in the PVN and by 50% in the anterior amygdaloid area, a control region of the brain. Taken together, these results indicate that 3-Br-7NI effectively inhibits maternal aggression and NO production in prairie voles and suggest that the central release of NO may play an important role in the production of maternal aggression in prairie voles.

Aggression↗

Can exercise therapy improve the outcome of microdiscectomy?

STUDY DESIGN: A prospective randomized controlled trial of exercise therapy in patients who underwent microdiscectomy for prolapsed lumbar intervertebral disc. Results of a pilot study are presented. OBJECTIVE: To determine the effects of a postoperative exercise program on pain, disability, psychological status, and spinal function. SUMMARY OF BACKGROUND DATA: Microdiscectomy is often used successfully to treat prolapsed lumbar intervertebral disc. However, some patients do not have a good outcome and many continue to have low back pain. The reasons for this are unclear but impairment of back muscle function due to months of inactivity before surgery may be a contributing factor. A postoperative exercise program may improve outcome in such patients. METHODS: Twenty patients who underwent lumbar microdiscectomy were randomized into EXERCISE and CONTROL groups. After surgery, all patients received normal postoperative care that included advice from a physiotherapist about exercise and a return to normal activities. Six weeks after surgery, patients in the EXERCISE group undertook a 4-week exercise program that concentrated on improving strength and endurance of the back and abdominal muscles and mobility of the spine and hips. Assessments of spinal function were performed in all patients during the week before surgery and at 6, 10, 26, and 52 weeks after. The assessment included measures of posture, hip and lumbar mobility, back muscle endurance capacity and electromyographic measures of back muscle fatigue. On each occasion, patients completed questionnaires inquiring about pain, disability and psychological status. RESULTS: Surgery improved pain, disability, back muscle endurance capacity and hip and lumbar mobility in both groups of patients. After the exercise program, the EXERCISE group showed further improvements in these measures and also in electromyographic measures of back muscle fatigability. All these improvements were maintained 12 months after surgery. The only further improvement showed by the CONTROL group between 6 and 52 weeks was an increase in back muscle endurance capacity. CONCLUSION: A 4-week postoperative exercise program can improve pain, disability, and spinal function inpatients who undergo microdiscectomy. [Key words: electromyogram median frequency, exercise therapy, intervertebral disc prolapse, microdiscectomy, randomized controlled trial, spinal function.

Adolescent↗

Maternal and mating-induced aggression is associated with elevated citrulline immunoreactivity in the paraventricular nucleus in prairie voles.

Lactating female rodents are fiercely aggressive against intruders when they are rearing and protecting pups. In monogamous prairie voles, Microtus ochrogaster, males are parental and exhibit a dramatic increase in aggression, termed mating-induced aggression, in association with reproduction. In mice, the gas, nitric oxide (NO), inhibits male aggression, but may have an excitatory role in the production of maternal aggression. In this study, we combined aggressive behavioral testing of female and male prairie voles with immunohistochemistry for citrulline, a marker of NO synthesis, to examine NO synthesis indirectly during maternal and mating-induced aggression. A significant increase in the number of citrulline-positive cells was identified in the paraventricular nucleus (PVN) of the hypothalamus in aggressive lactating females compared with unstimulated lactating females. A significant increase in the number of citrulline-positive cells was also observed in the PVN of aggressive mated males compared with nonaggressive unmated males and unstimulated mated males. Both nonaggressive unmated males and unstimulated mated males show similar levels of citrulline immunoreactivity in the PVN. In other regions of the brain, no changes in the number of citrulline-positive cells were observed. These results suggest that NO is released specifically in the PVN during both maternal and mating-induced aggression in prairie voles.

Aggression↗

A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice.

Although gangliosides are abundant molecular determinants on all vertebrate nerve cells (comprising approximately 1.5% of brain dry weight) their functions have remained obscure. We report that mice engineered to lack a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase), and which express only the simple ganglioside molecular species GM3 and GD3, develop significant and progressive behavioral neuropathies, including deficits in reflexes, strength, coordination, and balance. Quantitative indices of motor abilities, applied at 8 and 12 months of age, also revealed progressive gait disorders in complex ganglioside knockout mice compared to controls, including reduced stride length, stride width, and increased hindpaw print length as well as a marked reduction in rearing. Compared to controls, null mutant mice tended to walk in small labored movements. Twelve-month-old complex ganglioside knockout mice also displayed significant incidence of tremor and catalepsy. These comprehensive neurobehavioral studies establish an essential role for complex gangliosides in the maintenance of normal neural physiology in mice, consistent with a role in maintaining axons and myelin (Sheikh, K. A. , J. Sun, Y. Liu, H. Kawai, T. O. Crawford, R. L. Proia, J. W. Griffin, and R. L. Schnaar. 1999. Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc. Natl. Acad. Sci. USA 96: 7532-7537), and may provide insights into the mechanisms underlying certain neural degenerative diseases.

Animals↗

Maternal aggression in endothelial nitric oxide synthase-deficient mice.

Lactating female rodents protect their pups by expressing fierce aggression, termed maternal aggression, toward intruders. Mice lacking the neuronal nitric oxide synthase gene (nNOS-/-) exhibit significantly impaired maternal aggression, but increased male aggression, suggesting that nitric oxide (NO) produced by nNOS has opposite actions in maternal and male aggression. In contrast, mice lacking the endothelial nitric oxide synthase gene (eNOS-/-) exhibit almost no male aggression, suggesting that NO produced by eNOS facilitates male aggression. In the present study, maternal aggression in eNOS-/- mice was examined and found to be normal relative to wild-type (WT) mice in terms of the percentage displaying aggression, the average number of attacks against a male intruder, and the total amount of time spent attacking the male intruder. The eNOS-/- females also displayed normal pup retrieval behavior. Because a significant elevation of citrulline, an indirect marker of NO synthesis, occurs in neurons of the hypothalamus of lactating WT mice in association with maternal aggression, we examined the brains of eNOS-/- females for citrulline immunoreactivity following an aggressive encounter. The aggressive eNOS-/- females exhibited a significant elevation of citrulline in the medial preoptic nucleus and the subparaventricular zone of the hypothalamus relative to unstimulated lactating eNOS-/- females. Taken together, these results suggest that NO produced by eNOS neither facilitates nor inhibits maternal aggression and that NO produced by eNOS has a different role in maternal and male aggression.

Aggression↗

Annular abscesses in surgical endocarditis: anatomic, clinical, and operative features.

BACKGROUND: The aim of this study was to determine patterns of anatomic, clinical, and operative features in surgical endocarditis (SE) with annular abscess (AA). METHODS: The study consisted of a retrospective analysis of SE cases with AA between 1981 and 1997. RESULTS: A total of 41 cases with AA were found in 106 consecutive SE cases. There was a higher incidence of AA in aortic (37 of 71 [52%]) (p<0.01) compared to mitral (6 of 42 [14.3%]) or tricuspid (0 of 12) infections. However, the mitral abscesses had a greater tendency toward fistula or pseudoaneurysm formation (4 of 6 [67%]) than other valve abscess cavities (7 of 46 [15%]) (p<0.01). Severe heart failure (p<0.01), heart block (p<0.05), and fistula/pseudoaneurysm (p<0.001), were more often found in SE with AA than without. There were 46 separate aortic AA in 37 instances of aortic valve SE. Of these, 31 of 46 (67%) were less than 1 cm (group 1), 10 of 46 (22%) were large but confined to a given cusp annulus (group 2), 4 of 46 (8.6%) were large between multiple cusps (group 3), and 1 of 46 (2.2%) was circumferential (group 4). There were four instances of aortoventricular discontinuity. Group 1 abscesses were repaired by local closure without a patch significantly more often than the other groups. The mortality of SE with AA was significantly greater for larger AA (groups 3 and 4, 3 of 5 [60%]) than for smaller AA (groups 1 and 2, 0 of 36) (p<0.001). There were six separate mitral AA in six instances of mitral SE, five requiring patch repair. The 30-day operative mortality for AA cases was 3 of 41 (7.3%) compared to 2 of 65 (3.1%) without AA. All AA mortalities involved large AA in the aortic valve position. Of 35 mechanical valves placed for AA, only one required subsequent removal for prosthetic endocarditis. CONCLUSIONS: Annular abscesses are most frequent in aortic AA, but fistulas/pseudoaneurysms are more frequent in mitral AA. Small to moderate aortic AA can be managed by local closure without an increased mortality compared to SE without AA. Patients with large aortic AA have a higher operative mortality. Mechanical prostheses are safe and effective for the majority of patients with AA.

Abscess↗

In vitro melatonin treatment enhances splenocyte proliferation in prairie voles.

The seasonal effects of photoperiod on reproduction are mediated by melatonin, and it is hypothesized that increased immune function in short days is due to the increase in the duration of nightly melatonin secretion. Melatonin can act both directly and indirectly on target tissue within the immune system. The present study sought to tease apart the direct and indirect effects of melatonin on one aspect of immune function by examining the influence of in vitro melatonin on splenocyte proliferation in female prairie voles held in long (LD 16:8) or short (LD 8:16) days. Splenocyte proliferation in response to the T-cell mitogen concanavalin A was enhanced by the addition of melatonin in vitro, as compared to cultures receiving no melatonin. Body mass increased in short-day housed prairie voles, indicating that the animals were responsive to photoperiod. However, photoperiod did not affect splenocyte proliferation in the present study. These results support the hypothesis that melatonin exerts a direct effect on splenocyte proliferation, potentially via high-affinity melatonin receptors localized on splenocytes. The findings also indicate that, irrespective of photoperiod, melatonin exerts direct effects on splenocytes to enhance immune function.

Animals↗

Temperature and photoperiod interact to affect reproduction and GnRH synthesis in male prairie voles.

Prairie voles (Microtus ochrogaster), like most rodent species, exhibit a phenotypic polymorphism in reproductive response to winter conditions or to short day lengths in the laboratory. Laboratory studies on seasonally breeding species have traditionally focused on the role of photoperiod in modulating reproduction and other seasonal adaptions. However, because animals use proximate environmental factors in addition to photoperiod to phase seasonal adaptions with the appropriate time of year, the present study investigated the interaction of photoperiod and temperature on reproductive function and the gonadotropin-releasing hormone (GnRH) neuronal system. Male prairie voles were housed in either long (LD 16:8) or short (LD 8:16) photoperiods. Voles in each photoperiodic condition were also exposed to either mild (20 degrees C) or low (8 degrees C) temperatures. After 10 weeks, voles were killed and their brains were processed using in situ hybridization for mRNA for proGnRH. The results suggest that GnRH synthesis is not affected by exposure to a single inhibitory proximate factor (i.e. short days or low temperatures alone), even when reproduction is inhibited, whereas a combination of inhibitory proximate factors leads to a decrease in GnRH synthesis (i.e. fewer neurones staining for mRNA for proGnRH). These data suggest that the neuroendocrine mechanisms regulating seasonal alterations in reproductive function are likely to differ between harsh and mild winters.

Animals↗

Behaviour of near-infrared light in the adult human head: implications for clinical near-infrared spectroscopy.

To test theoretical assumptions supporting the use of near-infrared spectroscopy (NIRS) in clinical practice, we examined the behaviour of NIR light transmission and attenuation in the human head. Sterile probes for emitting and detecting NIR light at a fixed separation of 40 mm were placed in turn on intact skin, skull, dura and cerebral cortex of 10 patients undergoing elective neurosurgery. In the first five patients, the detecting probe was moved through successive extracerebral layers with the emitter on the skin surface. In the second five patients, the process was reversed, with the emitting probe moved and the detector in the same place on the scalp. NIR intensity was measured at each tissue interface and compared with the intensity measured at the skin surface with all layers intact. Removal of bone and dura from the light path caused a significant reduction in detected intensity. The largest mean reduction in light intensity was a 14-fold decrease with removal of bone (unadjusted P < 0.0001; paired t test). The assumptions that extracerebral tissues contribute little to attenuation of NIR light in the adult head and that most of this attenuation occurs superficially in the scalp are drawn into question by this study. We postulate that the skull and/or its interface with other layers may act as an optical 'channel', distorting the behaviour of NIR light in the human head.

Adult↗

Testicular regression in response to food restriction and short photoperiod in white-footed mice (Peromyscus leucopus) is mediated by apoptosis.

Short day lengths or reduced food availability are salient cues for small mammals that breed seasonally. Photoperiod-mediated gonadal regression in white-footed mice (Peromyscus leucopus) is a slow, orderly process that involves testicular apoptosis. Testicular regression in response to restricted caloric intake is relatively rapid, and it is generally reversed quickly by ad libitum (ad lib) feeding. To determine the contribution of apoptotic cell death during food restriction, and to examine possible interactions with photoperiod, mice housed in long (16L:8D) or short (8L:16D) photoperiods were fed either ad lib or 70% of their average ad lib intake. Testes were removed at 2, 4, 6, or 8 wk of experimental treatment. Apoptotic activity was determined by in situ TUNEL labeling and assessment of DNA laddering. Significant (P < 0.05) gonadal regression in response to short days was first detected at 8 weeks in mice fed ad lib. Food-restricted, long-day mice also showed significant testicular regression at 8 wk. Combined exposure to short day lengths and food restriction resulted in significant testicular regression at 6 wk (P < 0.05). TUNEL labeling was slightly, though significantly, elevated in germ cells at 2 and 4 wk in long-day food-restricted mice (P < 0.05). TUNEL labeling was also elevated in short-day food-restricted males at these early times but then increased nearly 5-fold at 6 and 8 wk in these mice (P < 0.001). DNA laddering confirmed elevated apoptosis. Overall apoptotic activity negatively correlated with paired testis mass, plasma testosterone, and spermatogenic index measurements in both ad lib and food-restricted males. Few histological markers of necrotic cell death were observed in any group. Taken together, these results suggest that testicular regression in response to limited caloric intake or short days is mediated by apoptosis.

Animals↗

Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse.

Recent findings in animals emphasize that experimental ischemic brain damage can be strikingly reduced by estrogen: however, the neuroprotective mechanisms are not well understood. It was hypothesized that estrogen signaling via cognate estrogen receptors (ERs) within the vasculature is an important aspect of cerebral ischemic protection in the female brain, in part by amplifying intraischemic cerebral blood flow (CBF). In the present study, the hypothesis that chronic treatment with the pure ER antagonist ICI182,780 (ICI) would increase ischemic brain damage by a blood flow-mediated mechanism was investigated. Adult C57B1/6J mice were pretreated with either subcutaneous ICI (100 microg/day) or oil/ethanol vehicle for 1 week before 2 hours of middle cerebral artery occlusion (MCAO) and 22 hours of reperfusion. End-ischemic regional CBF was evaluated in additional cohorts using [14C]iodoantipyrine autoradiography. Infarction volume as measured by cresyl violet histology was greater in the striatum of ICI-treated females (70 +/- 3% of contralateral striatum vs. 40 +/- 12% in vehicle-treated females). Cortical injury was not enhanced relative to control animals (39 +/- 6% of contralateral cortex in ICI group vs. 27 +/- 8% in vehicle-treated group). Physiologic variables and ischemic reduction of the ipsilateral cortical laser-Doppler flow signal were similar between groups. Further, ICI treatment did not alter end-ischemic cortical or striatal CBF. The deleterious effect of ICI was limited to females, as there were no differences in stroke damage or CBF between male treatment groups. These data suggest that estrogen inhibits ischemic brain injury in striatum of the female by receptor-mediated mechanisms that are not linked to preservation of intraischemic CBF.

Animals↗

Melatonin mediates seasonal changes in immune function.

Field studies indicate that immune function is compromised and the prevalence of many diseases are elevated during winter when energetic stressors are extensive. Presumably, individuals would enjoy a survival advantage if seasonally recurring stressors could be anticipated and countered by shunting energy reserves to bolster immune function. The primary environmental cue that permits physiological anticipation of season is daily photoperiod, a cue that is mediated by melatonin. However, other environmental factors, including low food availability and ambient temperatures, may interact with photoperiod to affect immune function and disease processes. This paper will review laboratory studies that consistently report enhanced immune function in short day lengths. Prolonged melatonin treatment mimics short days, and both in vitro and in vivo melatonin treatment enhances various aspects of immune function, especially cell-mediated immune function, in nontropical rodents. Reproductive responsiveness to melatonin appears to affect immune function. In sum, melatonin may be part of an integrative system to coordinate reproductive, immunologic, and other physiological processes to cope successfully with energetic stressors during winter.

Humans↗

Leptin, but not immune function, is linked to reproductive responsiveness to photoperiod.

Energetic demands are high while energy availability is minimum during winter. To cope with this energetic bottleneck, animals exhibit numerous energy-conserving adaptations during winter, including changes in immune and reproductive functions. A majority of individual rodents within a population inhibits reproductive function (responders) as winter approaches. A substantial proportion of small rodents within a species, however, fails to inhibit reproduction (nonresponders) during winter in the field or in the laboratory when maintained in winter-simulated day lengths. In contrast, immune function is bolstered by short day lengths in some species. The specific mechanisms that link reproductive and immune functions remain unspecified. Leptin is a hormone produced by adipose tissue, and several studies suggest that leptin modulates reproductive and immune functions. The present study sought to determine if photoperiodic alterations in reproductive function and leptin concentrations are linked to photoperiod-modulated changes in immune function. Siberian hamsters (Phodopus sungorus) were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 9 wk. After 9 wk, blood samples were collected during the middle of the light and dark phase to assess leptin concentrations. One week later, animals were injected with keyhole limpet hemocyanin to evaluate humoral immunity. Body mass, body fat content, and serum leptin concentrations were correlated with reproductive responsiveness to photoperiod; short-day animals with regressed gonads exhibited a reduction in these measures, whereas short-day nonresponders resembled long-day animals. In contrast, immune function was influenced by photoperiod but not reproductive status. Taken together, these data suggest that humoral immune function in Siberian hamsters is independent of photoperiod-mediated changes in leptin concentrations.

Adipose Tissue↗

Short photoperiods reduce vascular endothelial growth factor in the testes of Peromyscus leucopus.

Testicular regression in rodents occurs after short-day exposure. Vascular support is withdrawn during regression, and, presumably, new angiogenesis is inhibited. Blood vessel growth and maintenance are regulated by paracrine factors, including vascular endothelial growth factor (VEGF). Reduced angiogenesis may contribute to the onset of photoperiod-induced regression; i.e., reduction of VEGF protein would be detected early during gonadal atrophy. Alternatively, loss of blood vessel maintenance may reflect reduced testicular volume. If true, VEGF would not be expected to decline until significant regression occurred. To discriminate between these hypotheses, white-footed mice (Peromyscus leucopus) were maintained in either long (LD 16:8) or short (LD 8:16) photoperiod. Immunohistochemical and Western analyses revealed high VEGF expression in Leydig and Sertoli cells in long-day housed males and reduced VEGF expression in short-day housed males. Reductions in VEGF preceded decreases in both seminiferous tubule diameter and spermatogenic activity by 6 wk and reduced testis mass by 8 wk, suggesting that changes in VEGF are not a consequence of gonadal regression and that VEGF may play a critical role in photoperiodic regulation of testicular function.

Animals↗

Stroke in estrogen receptor-alpha-deficient mice.

BACKGROUND AND PURPOSE: Recent evidence suggests that endogenous estrogens or hormone replacement therapy can ameliorate brain damage from experimental stroke. Protective mechanisms involve enhanced cerebral vasodilation during ischemic stress as well as direct preservation of neuronal viability. We hypothesized that if the intracellular estrogen receptor subtype-alpha (ERalpha) is important to estrogen's signaling in the ischemic brain, then ERalpha-deficient (knockout) (ERalphaKO) female mice would sustain exaggerated cerebral infarction damage after middle cerebral artery occlusion. METHODS: The histopathology of cresyl violet-stained tissues was evaluated after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in ERalphaKO transgenic and wild-type (WT) mice (C57BL/6J background strain). End-ischemic cerebral blood flow mapping was obtained from additional female murine cohorts by using [(14)C]iodoantipyrine autoradiography. RESULTS: Total hemispheric tissue damage was not altered by ERalpha deficiency in female mice: 51.9+/-10.6 mm(3) in ERalphaKO versus 60.5+/-5.0 mm(3) in WT. Striatal infarction was equivalent, 12.2+/-1.7 mm(3) in ERalphaKO and 13.4+/-1.0 mm(3) in WT mice, but cortical infarction was paradoxically smaller relative to that of the WT (20.7+/-4.5 mm(3) in ERalphaKO versus 30.6+/-4.1 mm(3) in WT). Intraocclusion blood flow to the parietal cortex was higher in ERalphaKO than in WT mice, likely accounting for the reduced infarction in this anatomic area. There were no differences in stroke outcomes by region or genotype in male animals. CONCLUSIONS: Loss of ERalpha does not enhance tissue damage in the female animal, suggesting that estrogen inhibits brain injury by mechanisms that do not depend on activation of this receptor subtype.

Animals↗

Photoperiod and temperature interact to affect the GnRH neuronal system of male prairie voles (Microtus ochrogaster).

Individuals of numerous species limit energy expenditure during winter by inhibiting reproduction and other nonessential functions. To time these adaptations appropriately with the annual cycle, animals rely on environmental cues that predict, well in advance, the onset of winter. The most commonly studied environmental factor that animals use to time reproduction is photoperiod. Rodents housed in short photoperiods in the laboratory or in naturally declining day lengths exhibit pronounced alterations in reproductive function concomitant with alterations in the hypothalamic gonadotropin-releasing hormone neuronal system. Because animals in their natural environment use factors in addition to photoperiod to time reproduction, the present study sought to determine the independent effects of photoperiod and temperature, as well as the interaction between these factors, on reproductive parameters and the GnRH neuronal system. Male prairie voles were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 10 weeks. Animals in each photoperiod were further subdivided into groups housed in either mild (i.e., 20 degrees C) or low (i.e., 8 degrees C) temperatures. As shown with immunohistochemistry, voles that underwent gonadal regression in response to short photoperiods and long-day voles housed in low temperatures (and maintained large gonads) exhibit higher GnRH-immunoreactive (GnRH-ir) neuron numbers in the preoptic area/anterior hypothalamus (POA/AH) relative to all other groups. In addition, voles that underwent gonadal regression in response to both short days and low temperatures did not exhibit an increase in GnRH-ir neuron numbers compared to long-day, mild-temperature controls. These data suggest that photoperiod and temperature interact to influence reproductive function potentially by alterations of the GnRH neuronal system.

Acclimatization↗