Search for Daily Modulation of MeV Dark Matter Signals with DAMIC-M.

Dark matter (DM) particles with sufficiently large cross sections may scatter as they travel through Earth's bulk. The corresponding changes in the DM flux give rise to a characteristic daily modulation signal in detectors sensitive to DM-electron interactions. Here, we report results obtained from the first underground operation of the DAMIC-M prototype detector searching for such a signal from DM with MeV-scale mass. A model-independent analysis finds no modulation in the rate of 1 e^{-} events with sidereal period, where a DM signal would appear. We then use these data to place exclusion limits on DM in the mass range [0.53,2.7] MeV/c^{2} interacting with electrons via a dark photon mediator. Taking advantage of the time-dependent signal we improve by ∼2 orders of magnitude on our previous limit obtained from the total rate of 1 e^{-} events, using the same dataset. This daily modulation search represents the current strongest limit on DM-electron scattering via ultralight mediators for DM masses around 1 MeV/c^{2}.

First Constraints from DAMIC-M on Sub-GeV Dark-Matter Particles Interacting with Electrons.

We report constraints on sub-GeV dark matter particles interacting with electrons from the first underground operation of DAMIC-M detectors. The search is performed with an integrated exposure of 85.23 g days, and exploits the subelectron charge resolution and low level of dark current of DAMIC-M charge-coupled devices (CCDs). Dark-matter-induced ionization signals above the detector dark current are searched for in CCD pixels with charge up to 7e^{-}. With this dataset we place limits on dark matter particles of mass between 0.53 and 1000 MeV/c^{2}, excluding unexplored regions of parameter space in the mass ranges [1.6,1000] MeV/c^{2} and [1.5,15.1] MeV/c^{2} for ultralight and heavy mediator interactions, respectively.

Results on Low-Mass Weakly Interacting Massive Particles from an 11 kg d Target Exposure of DAMIC at SNOLAB.

We present constraints on the existence of weakly interacting massive particles (WIMPs) from an 11 kg d target exposure of the DAMIC experiment at the SNOLAB underground laboratory. The observed energy spectrum and spatial distribution of ionization events with electron-equivalent energies >200 eV_{ee} in the DAMIC CCDs are consistent with backgrounds from natural radioactivity. An excess of ionization events is observed above the analysis threshold of 50 eV_{ee}. While the origin of this low-energy excess requires further investigation, our data exclude spin-independent WIMP-nucleon scattering cross sections σ_{χ-n} as low as 3×10^{-41} cm^{2} for WIMPs with masses m_{χ} from 7 to 10 GeV c^{-2}. These results are the strongest constraints from a silicon target on the existence of WIMPs with m_{χ}<9 GeV c^{-2} and are directly relevant to any dark matter interpretation of the excess of nuclear-recoil events observed by the CDMS silicon experiment in 2013.

Constraints on Light Dark Matter Particles Interacting with Electrons from DAMIC at SNOLAB.

We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the DAMIC detector at SNOLAB of 2-6×10^{-22} A cm^{-2}. We evaluate the charge distribution of pixels that collect <10e^{-} for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c^{-2}. We also present new constraints on hidden-photon dark matter with masses in the range 1.2-30 eV c^{-2}.

Protein modelling to understand FGB mutations leading to congenital hypofibrinogenaemia.

INTRODUCTION: Congenital hypofibrinogenaemia is a quantitative fibrinogen disorder characterized by proportionally decreased levels of functional and antigenic fibrinogen. Mutations accounting for quantitative fibrinogen disorders are relatively frequent in the conserved COOH-terminal globular domains of the γ and Bß chains. The latter mutations are of particular interest since the Bß-chain is considered the rate-limiting chain in the hepatic production of the fibrinogen hexamer. AIM: The aim of this study was to study the molecular pattern of four patients with congenital hypofibrinogenaemia. METHODS: Four novel fibrinogen Bß-chain mutations leading to congenital hypofibrinogenaemia were identified in four women with heterogeneous symptoms. The human fibrinogen beta chain precursor protein sequence (P02675) was obtained from the UniProt database. The resulting models were analysed using swisspdbviewer 4.1.0. RESULTS: Three patients were heterozygous for different missense mutations located in the highly conserved ß nodule: c.882G>C:Arg294Ser (Arg264Ser), c.1298G>T:Trp433Leu (Trp403Leu) and c.1329C>G:Asn443Lys (Asn413Lys). Modelling analyses predicted major structural modifications likely to result in impaired fibrinogen secretion. One patient was heterozygous for an intron 7 donor splice mutation (c.1244 + 1G>A), leading to the complete abolishment of the donor site. CONCLUSIONS: Protein modelling of new causative mutations and comparison of molecular, biochemical and clinical data continue to yield valuable information on the development and course of fibrinogen disorders as well as on the choice of the most appropriate treatments.

Influence of external cooling on the femtosecond laser ablation of dentin.

In the present work, the influence of external cooling on the temperature rise in the tooth pulpal chamber during femtosecond laser ablation was investigated. The influence of the cooling method on the morphology and constitution of the laser-treated surfaces was studied as well. The ablation experiments were performed on dentin specimens using an Yb:KYW chirped-pulse-regenerative amplification laser system (560 fs, 1030 nm). Cavities were created by scanning the specimens at a velocity of 5 mm/s while pulsing the stationary laser beam at 1 kHz and with fluences in the range of 2-14 J/cm2. The experiments were performed in air and with surface cooling by a lateral air jet and by a combination of an air jet and water irrigation. The temperature in the pulpal chamber of the tooth was measured during the laser experiments. The ablation surfaces were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The temperature rise reached 17.5 °C for the treatments performed with 14 J/cm2 and without cooling, which was reduced to 10.8 ± 1.0 and 6.6 ± 2.3 °C with forced air cooling and water cooling, respectively, without significant reduction of the ablation rate. The ablation surfaces were covered by ablation debris and resolidified droplets containing mainly amorphous calcium phosphate, but the amount of redeposited debris was much lower for the water-cooled specimens. The redeposited debris could be removed by ultrasonication, revealing that the structure and constitution of the tissue remained essentially unaltered. The present results show that water cooling is mandatory for the femtosecond laser treatment of dentin, in particular, when high fluences and high pulse repetition rates are used to achieve high material removal rates.

Towards an MMP-2-activated molecular agent for cancer imaging.

Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential; however, non-invasive detection protocols are currently lacking. Herein, we describe the synthesis of a DOTA-containing peptide sequence that can be radiolabelled easily with 68Gallium or can be incorporated with gadolinium for possible MRI applications with clear selectivity for MMP-2 over other members of the MMP family, giving MMP-2 selective cleavage of the labelled peptides.

Association of A313 G polymorphism (GSTP1*B) in the glutathione-S-transferase P1 gene with sporadic Parkinson's disease.

Genetic predisposition, environmental toxins and aging contribute to Parkinson's disease (PD) multifactorial etiology. Weak environmental neurotoxic factors may accumulate over time increasing the disease risk in genetically predisposed subjects. Polymorphic genes encoding drug-metabolizing-enzymes (DMEs) are considered to account for PD susceptibility by determining individual toxic response variability. In this work, the allelic distributions and genotype associations of three major brain-expressed DMEs were characterized, in sporadic PD cases and controls. No significant association was found between CYP2D6 genotype and PD, but subjects with extensive metabolizer (EM) CYP2D6 phenotype, and the variant GSTP1*B genotype were at significantly higher PD risk than the corresponding poor or intermediary metabolizers (CYP2D6 poor metabolizer phenotype+intermediary metabolizers). A significant association was observed between the GSTP1*B allele and zygosity with PD (GSTP1*A/*B- 51.58%/34.37%, odds ratio (OR) = 2.29; 95% confidence interval (95% CI) = 1.25-4.18; *B/*B- 6.32%/1.05%, OR = 10.67; 95% CI = 1.19-94.79). This association was particularly strong in the elder patients group (> or =69 year) who showed double PD risk for GSTP1*B heterozygous, whilst GSTP1*B/*B homozygous were exclusively found amongst patients. An interaction between GSTM1 and GSTP1 was observed in this late onset PD group. The present results suggest that native GSTP1 encoding the fully active transferase variant should play a relevant role in dopaminergic neuroprotection.

Laser surface treatment of hydroxyapatite for enhanced tissue integration: surface characterization and osteoblastic interaction studies.

Biocompatibility has long been associated with surface microtopography, microtexture, and microchemistry. The surface topography eventually affects the nature and the intensity of the interactions that occur at biomaterial-biological interface (cell adhesion, mobility, spreading, and proliferation). Therefore, it is necessary to produce and work with controlled microtopographical surfaces that present reproducible microdomains of a dimension similar to that of the biological elements of interest (in this case, osteoblasts). There are a number of substrates that already have been studied in terms of surface topography; however, few studies are related to hydroxyapatite (HA) substrates. As it is well established, HA is a well-known ceramic that is extremely used in medical applications, namely implants and coatings. In this work, the surface topography of dense HA substrates was altered by using KFr excimer laser. The surface was characterized by atomic force microscopy and contact angle measurements, while the cell distribution and morphology was assessed by scanning electron microscopy and confocal laser scanning microscopy. Results revealed that the surface is characterized by a homogeneous columnar structure with high specific area. Moreover, cells were able to attach and spread on the surface of the samples, and gradually grow into nearly confluent monolayers.

Genetics, diagnosis and clinical features of congenital hypodysfibrinogenemia: a systematic literature review and report of a novel mutation.

Essentials Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders. This first systematic literature review led to identification of 51 hypodysfibrinogenemic cases. Diagnosis based only on functional/antigenic fibrinogen ratio may be insufficient. Family studies show an incomplete segregation of mutation with the clinical phenotypes. SUMMARY: Background Hypodysfibrinogenemia is a rare disease characterized by decreased levels of a dysfunctional fibrinogen. It shares features with both hypo- and dysfibrinogenemia, although with specific molecular patterns and clinical phenotypes. Objectives To better define the genetics, the diagnosis and the clinical features of hypodysfibrinogenemia. Patients/Methods A systematic literature search led to 167 records. After removal of duplicates, abstract screening and full-text reviewing, 56 molecular and/or clinical studies were analyzed, including a novel FGB missense mutation in a woman with a mild bleeding phenotype. Results A total of 32 single causative mutations were reported, mainly in the COOH-terminal region of the γ or Aα chains at heterozygous or homozygous state. Seven additional hypodysfibrinogenemias were due to compound heterozygosity. The hypofibrinogenemic phenotypes were a result of an impaired assembly or secretion or an increased clearance of the fibrinogen variant, whereas the dysfibrinogenemic phenotype was mainly a result of a defective fibrin polymerization and an abnormal calcium or tPA binding. Among 51 identified index cases, a functional/antigenic fibrinogen ratio < 0.7 had a sensitivity of 86% for the diagnosis of hypodysfibrinogenemia. Eleven patients (22%) were asymptomatic at time of diagnosis, 23 (45%) had a mild bleeding phenotype with mainly obstetrical or gynecologic-related hemorrhage and 22 (43%) had experienced at least one thrombotic event, including 23 venous and eight arterial thromboses. Conclusions This first systematic review on hypodysfibrinogenemia shows the heterogeneity of causative mutations and that misdiagnosis could occur in relation to the functional and antigenic fibrinogen levels. Family studies reveal an incomplete segregation of the mutation with the clinical phenotype.

[Neuropsychological impairment in patients with intracranial aneurysms: surgical versus endovascular treatment]. / Alteraciones neuropsicológicas en pacientes con aneurismas cerebrales: tratamiento quirúrgico versus tratamiento endovascular.

OBJECTIVES: To describe the neuropsychological status of patients with intracranial aneurysms and to compare the cognitive status of patients with intracranial aneurysm treated by surgical or endovascular methods. MATERIAL AND METHODS: Ninety-three cases with intracranial aneurysms treated with surgery (n = 56) or embolization (n = 37) were included. A neuropsychological assessment was applied to both groups retrospectively, at least one year after treatment. RESULTS: Neuropsychological impairment was found in both groups. 35.7% of the patients treated with surgery and 43.2%, of those treated with embolization did not show any cognitive impairment. Visual Memory and Cued Recall of verbal information are better in patients treated by embolization. CONCLUSIONS: Our results show that a large proportion of patients with intracranial aneurysms have cognitive impairment after treatment. Endovascular management may cause less impairment in visual and verbal memory. However, bleeding may be the most important factor to explain these cognitive impairments.

[Prevalence of type 2 diabetes in the preoperative assessment interview]. / Estudio de prevalencia de diabetes tipo 2 en una consulta de evaluación preoperatoria.

OBJECTIVES: To determine the prevalence of type 2 diabetes in preoperative anesthetic assessment interviews during May 2004 and to compare the results to prevalences reported in other studies. PATIENTS AND METHODS: Patients over the age of 20 years who received an assessment interview were included. Type 1 diabetics, pregnant women, and critically ill patients were excluded. We followed the 1997 diagnostic guidelines of the American Diabetes Association. RESULTS: The prevalence of previously diagnosed type 2 diabetes was 10.3%. Three patients were diabetics unaware of their disease. The overall prevalence of type 2 diabetes was 11% in this population. CONCLUSIONS: Type 2 diabetes has a high prevalence among surgical patients in our hospital, higher than that reported for the general population based on other studies.

Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by cine magnetic resonance imaging.

The capability of dynamic gradient-refocused magnetic resonance imaging (cine MRI) to detect, localize and functionally assess acute myocardial infarction (AMI) in 25 patients at a mean time interval of 7 days after AMI was evaluated. Fifteen asymptomatic volunteers were also examined to determine the specificity of the observations. Upon presentation, each patient received intravenous thrombolytic therapy, underwent immediate cardiac catheterization and had percutaneous transluminal coronary angioplasty performed when coronary reperfusion was absent. Twenty-four of the patients had documented coronary reperfusion at a mean interval of 259 +/- 129 minutes. Global ejection fraction and regional wall motion abnormalities were evaluated at 7 days by cine MRI, left ventriculography and radionuclide angiography. Twenty patients with both an absolute decrease in myocardial signal and a matched regional wall motion abnormality had AMI properly identified by cine MRI. In contrast, the finding of both decreased signal intensity and a matched regional wall motion abnormality was absent in the group of asymptomatic volunteers. The ejection fraction by cine MRI correlated better with the ejection fraction by left ventriculography (r = 0.94, standard error of the estimate = 3.6) than did the ejection fraction by radionuclide angiography (r = 0.82, standard error of the estimate = 5.8). The regional wall motion concordance rate in comparison to left ventriculography was similar for both cine MRI (69%) and radionuclide angiography (65%). These findings suggest that cine MRI may play an important role in the future detection and functional characterization of AMI.

Muscle activity localization with 31P spectroscopy and calculated T2-weighted 1H images.

Using 31P spectroscopy and magnetic resonance imaging (MRI), the authors studied changes in muscle phosphorous metabolites and T2 with isometric knee extension to evaluate the potential role of T2 images in coil placement for exercise spectroscopy studies. Increased signal intensity was visible in active muscles on T2 images after exercise. Calculated T2-weighted values were elevated immediately after exercise in the quadriceps (P less than .01). T2 increases for individual quadricep muscles varied, with the largest changes in the rectus femoris and the least in the vastus lateralis. 31P spectroscopy studies demonstrated similar findings: percent change in T2 correlated positively with inorganic phosphorus to phosphocreatine ratio (Pi/PCr) (r = 0.89, P less than .01) and negatively with pH (r = -0.88, P less than .01). The correlations between imaging and spectroscopy suggest that T2 images may allow more precise placement of phosphorous coils in exercise studies. The heterogeneity of T2 changes within the quadriceps with exercise suggests that assumptions about muscle activity may be misleading. T2 images may provide muscle activity verification for exercise studies.

Magnetic resonance imaging of blood flow with a phase subtraction technique. In vitro and in vivo validation.

RATIONALE AND OBJECTIVES: One promising approach to flow quantification uses the velocity-dependent phase change of moving protons. A velocity-encoding phase subtraction technique was used to measure the velocity and flow rate of fluid flow in a phantom and blood flow in volunteers. METHODS: In a model, the authors measured constant flow velocities from 0.1 to 270.0 cm/second with an accuracy (95% confidence intervals) of +/- 12.5 cm/second. There was a linear relationship between the magnetic resonance imaging (MRI) measurement and the actual value (r2 = .99; P = .0001). RESULTS: Measuring mean pulsatile flow from 125 to 1,900 mL/minute, the accuracy of the MRI pulsatile flow measurements (95% confidence intervals) was +/- 70 mL/minute. There was a linear relationship between the MRI pulsatile flow measurement and the actual value (r2 = .99; P = .0001). In 10 normal volunteers, the authors tested the technique in vivo, quantitating flow rates in the pulmonary artery and the aorta. The average difference between the two measurements was 5%. In vivo carotid flow waveforms obtained with MRI agreed well with the shape of corresponding ultrasound Doppler waveforms. CONCLUSIONS: Velocity-encoding phase subtraction MRI bears potential clinical use for the evaluation of blood flow. Potential applications would be in the determination of arterial blood flow to parenchymal organs, the detection and quantification of intra- and extra-cardiac shunts, and the rapid determination of cardiac output and stroke volume.

Production of Upsilon(1S) mesons from chi(b) decays in p&pmacr; collisions at sqrt

We have reconstructed the radiative decays chi(b)(1P)-->Upsilon(1S)gamma and chi(b)(2P)-->Upsilon(1S)gamma in p&pmacr; collisions at sqrt[s] = 1.8 TeV, and measured the fraction of Upsilon(1S) mesons that originate from these decays. For Upsilon(1S) mesons with p(Upsilon)(T)>8.0 GeV/c, the fractions that come from chi(b)(1P) and chi(b)(2P) decays are [27.1+/-6.9(stat)+/-4. 4(syst)]% and [10.5+/-4.4(stat)+/-1.4(syst)]%, respectively. We have derived the fraction of directly produced Upsilon(1S) mesons to be [50.9+/-8.2(stat)+/-9.0(syst)]%.

Search for a fourth-generation quark more massive than the Z0 boson in p&pmacr; collisions at radicals = 1.8 TeV

We present the results of a search for pair production of a fourth-generation charge -1 / 3 quark (b(')) in sqrt[s] = 1.8 TeV p&pmacr; collisions using 88 pb(-1) of data obtained with the Collider Detector at Fermilab. We assume that both quarks decay via the flavor-changing neutral current process b(')-->bZ(0) and that the b(') mass is greater than m(Z)+m(b). We studied the decay mode b(')b(');-->Z(0)Z(0)b&bmacr; where one Z0 decays into e(+)e(-) or &mgr;(+)&mgr;(-) and the other decays hadronically, giving a signature of two leptons plus jets. An upper limit on the sigma(p&pmacr;-->b(')b(');)x[B(b(')-->bZ(0))](2) is established as a function of the b(') mass. We exclude at 95% confidence level a b(') quark with mass between 100 and 199 GeV/c(2) for B(b(')-->bZ(0)) = 100%.

Transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region from p&pmacr; collisions at sqrt

The transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region of 66

Search for color singlet technicolor particles in p&pmacr; collisions at radicals = 1.8 TeV

We search for color singlet technirho and technipion production in p&pmacr; collisions at sqrt[s] = 1.8 TeV recorded with the Collider Detector at Fermilab. These exotic technimesons are present in a model of walking technicolor. The signatures studied are lepton plus two jets plus E(T) and multijet final states. No excess of events is seen in either final state. We set an upper limit on the technirho production cross section and exclude a region in the technipion mass versus technirho mass plane.