CP violation in the B system.

The phenomenon of CP violation is crucial to understand the asymmetry between matter and antimatter that exists in the Universe. Dramatic experimental progress has been made, in particular in measurements of the behaviour of particles containing the b quark, where CP violation effects are predicted by the Kobayashi-Maskawa mechanism that is embedded in the standard model. The status of these measurements and future prospects for an understanding of CP violation beyond the standard model are reviewed.

Psychiatric manifestations as initial presentation for pediatric CNS germ cell tumors, a case series.

BACKGROUND: Central nervous system (CNS) germ cell tumors account for 3 % of all pediatric brain tumors in the USA. Presenting symptoms are typically location based with pineal tumors presenting with obstructive hydrocephalus and suprasellar tumors with hypothalamic/pituitary dysfunction and ophthalmologic abnormalities. Psychiatric manifestations such as psychosis and behavioral changes are atypical presentations of CNS germ cell tumors, with only 11 previously reported cases. METHODS: This is a retrospective case series describing patients with CNS germ cell tumors with an atypical presentation including psychiatric manifestations. Information regarding clinical presentation, treatment course, and outcome were obtained. RESULTS: We report seven patients who presented with psychiatric symptoms consisting of psychomotor delay as well as behavioral and mood changes. Six of the seven patients were diagnosed ≥6 months after onset of psychiatric symptoms. All of the seven are alive but five continue to have neurologic and psychiatric issues post treatment. CONCLUSIONS: Atypical presentations of CNS germ cell tumors can delay diagnosis and treatment and may be secondary to atypical locations as well as endocrine dysfunction manifesting as psychiatric symptoms. Delayed diagnosis did not appear to affect survival but earlier diagnosis may potentially be associated with better neurologic and psychiatric outcome. Patients who present with these symptoms and atypical neuroimaging should have a thorough evaluation for CNS germ cell tumors including serum and CSF markers. Clinicians should be aware of these less common presentations to aid in prompt diagnosis and treatment.

The selective fabrication of large-area highly ordered TiO2 nanorod and nanotube arrays on conductive transparent substrates via sol-gel electrophoresis.

Large-area free-standing arrays of TiO(2) nanorods and nanotubes were selectively synthesized on transparent conducting indium tin oxide substrates using sol-gel electrophoresis and anodic alumina (AAO) thin film templates. The effect of sol-gel ageing on the growth of TiO(2) was explained, providing a tailored ability to produce nanotubes and nanorods. An annular tungsten base electrode, stemming from the anodization of the AAO template, was found to be crucial to the growth of nanotubes. This was supported by a study of substrate annealing in a reducing atmosphere. The work can be readily adapted for the fabrication of free-standing arrays of other metal, metal oxide, and complex oxide nanorod and nanotube arrays on conducting substrates.

The c-fos proto-oncogene is a target for transactivation by the p53 tumor suppressor.

The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting in inactivation of the wild-type (wt) p53 protein. The most notable biochemical feature of p53 is its ability to act as a sequence-specific transcriptional activator. Through use of the suppression subtractive hybridization differential screening technique, we identified c-fos as a target for transcriptional stimulation by p53 in cells undergoing p53-mediated apoptosis. Overexpression of wt p53 induces c-fos mRNA and protein. Moreover, in vivo induction of c-fos in the thymus following whole-body exposure to ionizing radiation is p53 dependent. p53 responsiveness does not reside in the basal c-fos promoter. Rather, a distinct region within the c-fos gene first intron binds specifically to p53 and confers upon the c-fos promoter the ability to become transcriptionally activated by wt p53. Identification of c-fos as a specific target for transcriptional activation by p53 establishes a direct link between these two pivotal regulatory proteins and raises the possibility that c-fos contributes to some of the biological effects of p53.

The Mdm2 oncoprotein interacts with the cell fate regulator Numb.

The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate. This association causes translocation of overexpressed Numb into the nucleus and leads to a reduction in overall cellular Numb levels. Through its interaction with Numb, Mdm2 may influence processes such as differentiation and survival. This could potentially contribute to the altered properties of tumor cells which overexpress Mdm2.

Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation.

Correction to: Oncogene (2013) 32, 2304­2314; doi:10.1038/onc. 2012.248; published online 18 June 2012. Since the publication of the above paper, the author listed as C Ryan Miller has requested that the listing of his name be changed to CR Miller.

ASC deficiency suppresses proliferation and prevents medulloblastoma incidence.

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC's role in most cancers remains unknown. Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer; ASC is also expressed in human medulloblastomas. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and a delayed tumor onset. A similar decrease in tumorigenesis with ASC deficiency was also seen in the hGFAP-Cre:SmoM2 mouse model of medulloblastoma. Interestingly, hyperproliferation of the external granule layer (EGL) was comparable at P20 in both wild-type and ASC-deficient SmoA1 mice. However, while the apoptosis and differentiation markers remained unchanged at this age, proliferation makers were decreased, and the EGL was reduced in thickness and area by P60. This reduction in proliferation with ASC deficiency was also seen in isolated SmoA1 cerebellar granule precursor cells in vitro, indicating that the effect of ASC deletion on proliferation was cell autonomous. Interestingly, ASC-deficient SmoA1 cerebella exhibited disrupted expression of genes in the transforming growth factor-ß pathway and increased level of nuclear Smad3. Taken together, these results demonstrate an unexpected role for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for antitumor therapy.

Prescribing books for immigrant children: a pilot study to promote emergent literacy among the children of Hispanic immigrants.

OBJECTIVES: To assess book-sharing activities within first-generation Hispanic immigrant families, and to assess the effect of pediatricians giving books to their patients. DESIGN: Survey. PARTICIPANTS: Convenience sample of 122 predominantly Hispanic immigrant parents of children aged 2 months to 5 years. Of these parents, 56 had received children's books from the pediatrician, and 66 had not. SETTING: House staff continuity clinic at a university children's hospital. MAIN OUTCOME MEASURE: Frequent Book Sharing (FBS) was defined as a parent's reporting more than 3 days per week of sharing books with the child. Main independent variables included the following: (1) exposure to the Reach Out and Read program, defined as having received a children's book from the pediatrician; (2) socioeconomics, as measured by parents' years of education and Medicaid enrollment; (3) acculturation, as defined by 4 questions relating to parents' proficiency with the English language; (4) parent's country of origin; (5) parent literacy, as measured by a parent's reporting more than 3 days per week of reading alone; (6) parent's age; (7) marital status; (8) household size; (9) child's age; (10) child's sex. RESULTS: Ninety percent of the parents were born outside of the United States (71% in Mexico), 85% spoke Spanish in the home, and 63% had completed less than a high-school education. Seventy-five percent of children's medical insurance was provided by Medi-Cal (Medicaid), and 9% of children were uninsured. Sixty-seven percent spoke exclusively Spanish at home, and 84% of parents want their children to learn to read in both English and Spanish. High FBS was reported among parents whose children had received books from the physician when compared with parents whose children had received no books. The odds ratio (OR) was 3.62 (95% confidence interval [CI], 1.40-9.37; P<.05). Also associated with FBS were parents reading frequently to themselves (OR = 9.52; 95% CI, 2.09-43.27; P<.05) and national origin outside Mexico (OR = 5.54; 95% CI, 1.59-19.27; P<.05). These findings were independent of parent's educational level, parent's employment, parent's age, acculturation, and family size. CONCLUSIONS: Pediatricians can promote literacy development among Hispanic immigrant children through the provision of free books at well-child visits. Our findings also suggest the independent effects of adult literacy and child age. Further research is needed to understand the effect of pediatric literacy programs on Hispanic immigrant children, their bilingual environments, and their readiness for school entry. Arch Pediatr Adolesc Med. 2000;154:771-777

Dermatoglyphic study in autistic children and controls.

Dermatoglyphic patterns formed during fetal development reflect genetic or early developmental events. These patterns might provide a means for investigation of a biological basis for autism, but the results of prior studies are not conclusive. The authors undertook a study of 95 autistic children, defined by DSM-III criteria ascertained independently by three child psychiatrists. The dermatoglyphic patterns of these children were compared with several control groups, all age-matched, separated by sex, and comprising different ethnic compositions. Analysis of variance as well as chi-square methods of statistical analysis were applied. Consistency among hands, ATD angle values, total ridge counts, incidence and effects on ridge count of arches, double loops, and whorls were evaluated in this comparatively large, well-controlled group of autistic children, and all failed to support a value for dermatoglyphic analysis as a discriminant of autism.

Stigmatization, self-esteem, and coping among the adolescent children of lesbian mothers.

PURPOSE: To examine perceived stigma, coping, disclosure, and self-esteem among adolescents with lesbian mothers. METHOD: Interviews were conducted with 76 adolescents ages 11-18 years. Standardized measures of self-esteem and coping skills were used. A measure of stigma was adapted for this study and a measure of disclosure was developed. The relationship between perceived stigma and self-esteem was examined. General coping skills and level of disclosure about the adolescents' mothers' sexual orientation were assessed as potential moderators of the relationship between perceived stigma and self-esteem. RESULTS: Adolescents who perceived more stigma had lower self-esteem in five of seven self-esteem areas, compared to those who perceived less stigma. In addition, coping skills moderated the effect of stigma on self-esteem in three self-esteem areas. However, only one subtype of coping skills, that of decision-making coping, was found to moderate the relationship of perceived stigma and self-esteem in such a way that adolescents using more decision-making coping had higher self-esteem in the face of high perceived stigma. For social support coping, in the face of high perceived stigma, the adolescents with more effective coping skills had lower self-esteem. In the face of high perceived stigma, adolescents who disclosed more about their mother's sexual orientation had higher self-esteem in the subscale of close friendship than those who disclosed less. CONCLUSIONS: Results suggest that stigma is related to self-esteem among the adolescent children of lesbian mothers. The results indicate that this relationship is moderated by coping skills. These results have implications for intervention and prevention of stigmatization by the establishment of effective coping skills as well as through educational efforts to eradicate stigmatizing attitudes.

Delayed cardiac tamponade after pacemaker insertion.

Cardiogenic shock is one of the most dramatic presentations in Emergency Medicine and requires rapid and accurate assessment, evaluation, and treatment. The cardiovascular disasters that present with shock include acute myocardial infarction with pump failure, aortic dissection, massive pulmonary emboli, and cardiac tamponade. We report a patient who presented to our Emergency Department (ED) in cardiogenic shock 10 days after insertion of a permanent cardiac pacemaker. The patient had developed pericardial tamponade secondary to the insertion. In reviewing the literature, we found many reports relating to complications of pacemakers and even more information regarding the various etiologies of cardiac tamponade, but cardiac tamponade as a consequence of pacemaker insertion rarely has been reported. Cardiac tamponade can occur secondary to perforation of the right ventricle during pacemaker electrode insertion and manipulation. Perforation is generally believed to be benign and self-limiting and only rarely causes tamponade and hemodynamic compromise; however, that was not the case for our patient.

Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation.

Neurogenesis requires negative regulation through differentiation of progenitors or their programmed cell death (PCD). Growth regulation is particularly important in the postnatal cerebellum, where excessive progenitor proliferation promotes medulloblastoma, the most common malignant brain tumor in children. We present evidence that PCD operates alongside differentiation to regulate cerebellar granule neuron progenitors (CGNPs) and to prevent medulloblastoma. Here, we show that genetic deletion of pro-apoptotic Bax disrupts regulation of cerebellar neurogenesis and promotes medulloblastoma formation. In Bax(-/-) mice, the period of neurogenesis was extended into the third week of postnatal life, and ectopic neurons and progenitors collected in the molecular layer of the cerebellum and adjacent tectum. Importantly, genetic deletion of Bax in medulloblastoma-prone ND2:SmoA1 transgenic mice greatly accelerated tumorigenesis. Bax-deficient medulloblastomas exhibited strikingly distinct pathology, with reduced apoptosis, increased neural differentiation and tectal migration. Comparing Bax(+/+) and Bax(-/-) medulloblastomas, we were able to identify upregulation of Bcl-2 and nuclear exclusion of p27 as tumorigenic changes that are required to mitigate the tumor suppressive effect of Bax. Studies on human tumors confirmed the importance of modulating Bax in medulloblastoma pathogenesis. Our results demonstrate that Bax-dependent apoptosis regulates postnatal cerebellar neurogenesis, suppresses medulloblastoma formation and imposes selective pressure on tumors that form. Functional resistance to Bax-mediated apoptosis, required for medulloblastoma tumorigenesis, may be a tumor-specific vulnerability to be exploited for therapeutic benefit.

Observation of direct CP violation in B0 --> pi+pi- decays and model-independent constraints on the quark-mixing angle phi2.

We report a new measurement of the time-dependent CP-violating parameters in B(0)-->pi(+)pi(-) decays with 535 x 10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider operating at the Upsilon(4S) resonance. We find 1464+/-65 B(0)-->pi(+)pi(-) events and measure the CP-violating parameters S(pipi)=-0.61+/-0.10(stat)+/-0.04(syst) and A(pipi)=+0.55+/-0.08(stat)+/-0.05(syst). We observe large direct CP violation with a significance greater than 5 standard deviations for any S(pipi) value. Using isospin relations, we measure the Cabibbo-Kobayashi-Maskawa quark-mixing matrix angle phi(2)=(97+/-11) degrees for the solution consistent with the standard model and exclude the range 11 degrees

Measurement of CP asymmetry in a time-dependent Dalitz analysis of B0-->(rhopi)0 and a constraint on the quark mixing matrix angle phi2.

We present a measurement of CP asymmetry using a time-dependent Dalitz plot analysis of B0-->pi+pi-pi0 decays based on a 414 fb(-1) data sample containing 449 x 10(6) BB pairs. The data was collected on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric energy e+ e- collider. Combining our analysis with information on charged B decay modes, we perform a full Dalitz and isospin analysis and obtain a constraint on the CKM angle phi2, 68 degrees < phi2 < 95 degrees as the 68.3% confidence interval for the phi2 solution consistent with the standard model (SM). A large SM-disfavored region also remains.

Experimental constraints on the spin and parity of the Lambdac(2880)+.

We report the results of several studies of the Lambda(c)(+)pi(+)pi(-)X final state in continuum e(+)e(-) annihilation data collected by the Belle detector. An analysis of angular distributions in Lambda(c)(2880)(+)-->Sigma(c)(2455)(0,++)pi(+,-) decays strongly favors a Lambda(c)(2880)(+) spin assignment of 5/2 over 3/2 or 1/2. We find evidence for Lambda(c)(2880)(+)-->Sigma(c)(2520)(0,++)pi(+,-) decay and measure the ratio of Lambda(c)(2880)(+) partial widths Gamma(Sigma(c)(2520)pi)/Gamma(Sigma(c)(2455)pi)=0.225+/-0.062+/-0.025. This value favors the Lambda(c)(2880)(+) spin-parity assignment of 5/2(+) over 5/2(-). We also report the first observation of Lambda(c)(2940)(+)-->Sigma(c)(2455)(0,++)pi(+,-) decay and measure Lambda(c)(2880)(+) and Lambda(c)(2940)(+) mass and width parameters. These studies are based on a 553 fb(-1) data sample collected at or near the Upsilon(4S) resonance at the KEKB collider.

Measurement of the tau lepton mass and an upper limit on the mass difference between tau+ and tau-.

The mass of the tau lepton has been measured in the decay mode tau-->3pinutau using a pseudomass technique. The result obtained from 414 fb-1 of data collected with the Belle detector is Mtau=[1776.61+/-0.13(stat)+/-0.35(sys)] MeV/c2. The upper limit on the relative mass difference between positive and negative tau leptons is |Mtau+-Mtau-|/Mtau<2.8 x 10-4 at 90% confidence level.

Measurement of inclusive Ds, D0, and J/psi rates and determination of the Bs(*)Bs(*) production fraction in bb Events at the Upsilon(5S) resonance.

The inclusive production of D(s), D(0), and J/psi mesons is studied using a 1.86 fb(-1) data sample collected on the Upsilon(5S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The number of bb events in this Upsilon(5S) data sample is determined. We measure the branching fractions B(Upsilon(5S)-->D(s)X)/2=(23.6+/-1.2+/-3.6)%, B(Upsilon(5S)-->D(0)X)/2=(53.8+/-2.0+/-3.4)%, and B(Upsilon(5S)-->J/psiX)/2=(1.030+/-0.080+/-0.067)%. From the D(s) and D(0) inclusive branching fractions the ratio f(s)=(18.0+/-1.3+/-3.2)% of B(s)(*)B(s)(*) to the total bb quark pair production at the Upsilon(5S) energy is obtained in a model-dependent way.

Observation of a charmoniumlike state produced in association with a J/psi in e+e- annihilation at sqrt[s] approximately equal to 10.6 GeV.

We report the first observation of a charmoniumlike state recoiling from the J/psi in the inclusive process e+e- -->J/psi+anything at a mass of (3.943+/-0.006+/-0.006) GeV/c{2}. We also observe the decay of this state into D*D[over ] and determine its intrinsic width to be less than 52 MeV/c{2} at the 90% C.L. These results are obtained from a 357 fb{-1} data sample collected with the Belle detector near the Upsilon(4S) resonance, at the KEKB asymmetric-energy e+e- collider.

Measurement of the near-threshold e+e- --> D(*)+/-D(*)-/+ cross section using initial-state radiation.

We report a measurement of the exclusive e+e- -->D(*)+/-D*-/+ cross section as a function of center-of-mass energy near the D(*)+/-D*-/+ threshold with initial-state radiation. A partial reconstruction technique is used to increase the efficiency and to suppress background. The analysis is based on a data sample collected with the Belle detector with an integrated luminosity of 547.8 fb(-1).