Remarks on sum rules in the heavy quark limit of QCD

We underline a problem existing in the heavy quark limit of QCD concerning the rates of semileptonic B decays into P-wave $D_J(j)$ mesons, where $j = {1 \over 2}$ (wide states) or $j = {3 \over 2}$ (narrow states). The leading order sum rules of Bjorken and Uraltsev suggest $\Gamma [ \bar{B} \to D_{0,1} ({1 \over 2}) \ell \nu ] \ll \Gamma [ \bar{B} \to D_{1,2} ({3 \over 2}) \ell \nu ]$, in contradiction with experiment. The same trend follows also from a sum rule for the subleading $1/m_Q$ curent matrix element correction $\xi_3(1)$. The problem is made explicit in relativistic quarks models \`a la Bakamjian and Thomas, that give a transparent physical interpretation of the latter as due, not to a $L \cdot S$ force, but to the Wigner rotation of the light quark spin. We point out moreover that the selection rule for decay constants of $j = {3 \over 2}$ states, $f_{3/2} = 0$, predicts, assuming the model of factorization, the opposite hierarchy $\Gamma [ \bar{B} \to \bar{D}_{s_{1,2}} ({3 \over 2}) D^{(*)} ] \ll \Gamma [ \bar{B} \to \bar{D}_{s_{0,1}} ({1 \over 2}) D^{(*)} ]$.Comment: Contribution to the International Europhysics Conference on HEP, Budapest, July 2001 (presented by L. Oliver); 5 page

CDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Cancer

BACKGROUND. CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. METHODS. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. RESULTS. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CONCLUSION. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.Department of Defense Breast Cancer Research Program (DAMD 17-99-1-9573); National Institutes of Health PHS (CA081078); LaPann Fun

Quantitative predictions for B semileptonic decays into D, D*, and the orbitally excited D** in quark models in the manner of Bakamjian and Thomas

Once chosen the dynamics in one frame, the rest frame in this paper, the Bakamjian and Thomas method allows to define relativistic quark models in any frame. These models have been shown to provide, in the infinite quark mass limit, fully covariant current form factors as matrix elements of the quark current operator. In this paper we use the rest frame dynamics fitted from the meson spectrum by various authors, already shown to provide a reasonable value for $\rho^2$. From the general formulae for the scaling invariant form factors $\xi^{(n)}(w)$, $\tau_{1/2}^{(n)}(w)$ and $\tau_{3/2}^{(n)}(w)$, we predict quantitavely the $B$ semileptonic branching ratios to the ground state and orbitally excited charmed mesons $D, D^\ast$ and $D^{\ast\ast}$. We check Bjorken's sum rule and discuss the respective contributions to it. We find $\xi(w)\simeq (2/(1+w)) ^2$, resulting from the fact that the ground state wave function is Coulomb-like. We also find $\tau_{3/2}\simeq 0.5 (2/(1+w))^3$ and $\tau_{1/2}(w)\ll \tau_{3/2}(w)$. Very small branching ratios into $j=1/2$ orbitally excited $D$'s results. The overall agreement with experiment is rather good within the present accuracy which is poor for the orbitally excited charmed mesons. We predict a ratio $Br(B\to D^\ast_2 l \nu)/Br(B\to D_1 l \nu)=1.55\pm 0.15$ as a mere consequence of the heavy quark symmetry. If some faint experimental indications that $Br(B\to D_1 l \nu)\simeq Br(B\to D^\ast_2 l \nu)$ were confirmed, it would indicate a sizeable $O(1/m_c)$ correction

Duality in semileptonic inclusive B-decays in potential models: regular versus singular potentials

International audienceMaking use of the nonrelativistic potential model for the description of mesons, and working in the Shifman–Voloshin limit, we compare the integrated rate Γ (B → X c lν) calculated as a sum of the individual decay rates to the quantum-mechanical analog of the OPE. In the case of a potential regular at the origin, we find a well-defined duality violation, which is, however, exponentially small. It corresponds to the charm resonances kinematically forbidden in the decay process, but apparently picked up by the OPE. For singular potentials, we do not obtain a full OPE series, but only a limited Taylor expansion, since the coefficients become infinite beyond some order. In this case, we do not find an indication of duality violation: the difference is smaller than the last term of the limited expansion. This emphasizes that the case of singular potentials, which may be relevant for QCD, deserves further study. 2001 Published by Elsevier Science B.V

apeNEXT: A multi-TFlops Computer for Simulations in Lattice Gauge Theory

We present the APE (Array Processor Experiment) project for the development of dedicated parallel computers for numerical simulations in lattice gauge theories. While APEmille is a production machine in today's physics simulations at various sites in Europe, a new machine, apeNEXT, is currently being developed to provide multi-Tflops computing performance. Like previous APE machines, the new supercomputer is largely custom designed and specifically optimized for simulations of Lattice QCD.Comment: Poster at the XXIII Physics in Collisions Conference (PIC03), Zeuthen, Germany, June 2003, 3 pages, Latex. PSN FRAP15. Replaced for adding forgotten autho

Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration

BACKGROUND: The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. METHODS: We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer's disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years). RESULTS: Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen's f2 = 0.137) and memory decline (p = 0.006, Cohen's f2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen's f2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1-42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group. CONCLUSION: Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD

Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer\u27s disease: A longitudinal observational study

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer\u27s disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer\u27s pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer\u27s disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer\u27s disease. METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer\u27s disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR\u3e0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=-4·28 × 10 INTERPRETATION: Our findings in autosomal dominant Alzheimer\u27s disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing. FUNDING: German Research Foundation, US National Institutes of Health

Destructive breakdown studies of irradiated LGADs at beam tests for the ATLAS HGTD

In the past years, it has been observed at several beam test campaigns that irradiated LGAD sensors break with a typical star shaped burn mark when operated at voltages much lower than those at which they were safely operated during laboratory tests. The study presented in this paper was designed to determine the safe operating voltage that these sensors can withstand. Many irradiated sensors from various producers were tested in two test beam facilities, DESY (Hamburg) and CERN-SPS (Geneva), as part of ATLAS High Granularity Timing Detector (HGTD) beam tests. The samples were placed in the beam and kept under bias over a long period of time in order to reach a high number of particles crossing each sensor. Both beam tests lead to a similar conclusion, that these destructive events begin to occur when the average electric field in the sensor becomes larger than 12 Volts per micrometre.Comment: Published versio

Different pattern of CSF glial markers between dementia with Lewy bodies and Alzheimer's disease

The role of innate immunity in dementia with Lewy bodies (DLB) has been little studied. We investigated the levels in cerebrospinal fluid (CSF) of glial proteinsYKL-40, soluble TREM2 (sTREM2) and progranulin in DLB and their relationship with Alzheimer's disease (AD) biomarkers. We included patients with DLB (n = 37), prodromal DLB (prodDLB, n= 23), AD dementia (n = 50), prodromal AD (prodAD, n= 53), and cognitively normal subjects (CN, n= 44).We measured levels ofYKL-40, sTREM2, progranulin, A beta(1-42), total tau (t-tau) and phosphorylated tau (p-tau) in CSF. We stratified the group DLB according to the ratio t-tau/A beta(1-42 ) (>= 0.52, indicative of AD pathology) and the A/T classification. YKL-40, sTREM2 and progranulin levels did not differ between DLB groups and CN.YKL-40 levels were higher in AD and prodAD compared to CN and to DLB and prodDLB. Patients with DLB with a CSF profile suggestive of AD copathology had higher levels of YKL-40, but not sTREM2 or PGRN, than those without. T+ DLB patients had also higherYKL-40 levels than T-. Of these glial markers, onlyYKL-40 correlated with t-tau and p-tau in DLB and in prodDLB. In contrast, in prodAD, sTREM2 and PGRN also correlated with t-tau and p-tau. In conclusion, sTREM2 and PGRN are not increased in the CSF of DLB patients. YKL-40 is only increased in DLB patients with an AD biomarker profile, suggesting that the increase is driven by AD-related neurodegeneration. These data suggest a differential glial activation between DLB and AD

Covariant Light-Front Approach for s-wave and p-wave Mesons: Its Application to Decay Constants and Form Factors

We study the decay constants and form factors of the ground-state s-wave and low-lying p-wave mesons within a covariant light-front approach. Numerical results of the form factors for transitions between a heavy pseudoscalar meson and an s-wave or p-wave meson and their momentum dependence are presented in detail. In particular, form factors for heavy-to-light and B to D** transitions, where D** denotes generically a p-wave charmed meson, are compared with other model calculations. The experimental measurements of the decays B^- to D** pi^- and B to D D**_s are employed to test the decay constants of D**_s and the B to D** transition form factors. The heavy quark limit behavior of the decay constants and form factors is examined and it is found that the requirement of heavy quark symmetry is satisfied. The universal Isgur-Wise (IW) functions, one for s-wave to s-wave and two for s-wave to p-wave transitions, are obtained. The values of IW functions at zero recoil and their slope parameters can be used to test the Bjorken and Uraltsev sum rules.Comment: 59 pages, 6 figures. Version to appear in Phys. Rev. D. Changes are: (i) D_s to phi transition form factors are discussed and compared with the recent FOCUS measurements and (ii) zero mode effects are clarifie