Autism spectrum disorders (ASDs) now affect 1–2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg−1 intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl−1 (±0.50) and 5.15 pmol mg−1 (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults.

III-V FETs are being developed for potential application in 0.3-3 THz systems and VLSI. To increase bandwidth, we must increase the drive current I d = qns v in j� per unit gate width Wg, requiring both high sheet carrier concentrations n , and high injection velocities vin. Present III-V NFETs restrict control region transport to the single isotropic r band minimum. As the gate dielectric is thinned, I d becomes limited by the effective mass m * , and is only increased by using materials with increased m * and hence increased transit times. 1 The deep wavefunction also makes r -valley transport in low-m * materials unsuitable for < 22-nm gate length ( Lg ) FETs.Yet, the L-valleys in many III-V materials2 have very low transverse m, and very high longitudinal mass mi' L valley bound state energies depend upon orientation, and the directions of confmement, growth, and transport can be chosen to selectively populate valleys having low mass in the transport direction3,4. The high perpendicular mass permits placement of multiple quantum wells spaced by a few nm, or population of multiple states of a thicker well spaced by -10-100 me V. Using combinations of r and L valleys, n , can be increased, m * kept low, and vertical confmement improved, key requirements for <20-nm Lg III-V FETs.Consider FET scaling. To increase bandwidth r :1, capacitances and transit delays must be reduced r:1 while maintaining constant voltages, currents, and resistances. In short-Lg FETs, the gate-source Cgs . ! oc sWg and gate drain Cgd oc s� fringing capacitances are a significant fraction of the total capacitance, and limit!,. Cgs . ! and Cgd are only weakly dependent on lateral geometry, hence the (Cg S ,f + Cgd)� V I Iddelay is reduced r:1 only if Id IWgis increased r:1. Id is determined by the sheet carrier concentration n , = ( Cg_ch I Lg � X � s -Vii.) I q, where the gate channel capacitance Cg_ ch = [1/ Cox + 1/ Cdep/h + 1/ C D ost is the series combination ot dielectric Cox = ss tO, Lg� ITeq' wavefunction depth Cdep/h = ssemiLg� I Tin v (T in V is the wavefunction mean depth) and density of states Cdos = q2 . dns I dEf capacitances. In the ballistic case, Cdos = q2 g(ml l molyl2 Lg� 127Tit 2 , where g is the # of populated valleys, and mi l and mol the effective masses parallel and perpendicular to transport; near equilibrium, Cdosis 2:1 larger.Given ballistic transporf andEf-EweJ1»kT, vin j = (4/37!X2(Ef-E...., )lml l Y'2 =( 4/37!X2qCg_ch ( � S -V/h)l m-,Pdoy2 . We scale by maintaining constant Vin j while reducing Cox I LgWg' Cdep/h I LgWg' and Cd . .! Lg� by r:1 This requires fixed transport mass mi l ' T eq and Tin V reduced r :1, and C dos increased r : 1 by increasing the # of valleys or the perpendicular mass.At a given dielectric thickness T eq ulv , there is an o p timum m * maximizing I d' We fmd I d I� =Jo ·K 1 ·«�s -V/h )11V)31 2 , where Jo = (41 371X2q I moyl2 V Vt\q2 mo I 27Tit 2 ) = 84 mA/J.m and K I = n . (mol Im . ) 1 1 2 (1 + (Cdos,o ICeqvulv) ' g ' (m�2 m:i2 I m.)r312is the normalized current density. Ceq U Iv = ...

Summary Background Glucocorticoids (GCs) are generally envisioned as immunosuppressive, but in conditions such as rosacea and perioral dermatitis they can lead to increased skin inflammation. In lung epithelia, GCs promote expression of the proinflammatory cytokine CCL20, which contributes to steroid‐resistant asthma. In the skin, CCL20 stimulates inflammation by recruiting T helper 17 T lymphocytes and dendritic cells, and is elevated in papulopustular rosacea. Objectives To understand if, and how, GCs affect CCL20 expression in human keratinocytes. CCL20 expression was assessed by quantitative reverse transcriptase polymerase chain reaction and enzyme‐linked immunosorbent assay. Methods Selective inhibition of candidate genes and signalling pathways was performed using RNA interference and chemical inhibitors. The binding of activated GC receptor to genomic DNA was determined by chromatin immunoprecipitation, and enhancer activity of genomic sequences was measured with a reporter assay. Results We found that GC treatment increased CCL20 expression in human keratinocytes and murine skin, both in the undisturbed state and with tumour necrosis factor‐α stimulation. GC repressed proinflammatory signalling pathways, including nuclear factor kappa B and p38/mitogen‐activated protein kinase, but these inhibitory effects were opposed by the direct binding of activated GC receptor to the CCL20 enhancer, promoting CCL20 expression. Conclusions Viewed together, these findings demonstrate a mechanism by which GCs induce expression of CCL20 in keratinocytes, which may contribute to the inflammation seen in steroid‐exacerbated skin conditions.