Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

H.E.S.S. Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center.

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

Combined Atomic Force Microscope and Volumetric Light Sheet System for Correlative Force and Fluorescence Mechanobiology Studies.

The central goals of mechanobiology are to understand how cells generate force and how they respond to environmental mechanical stimuli. A full picture of these processes requires high-resolution, volumetric imaging with time-correlated force measurements. Here we present an instrument that combines an open-top, single-objective light sheet fluorescence microscope with an atomic force microscope (AFM), providing simultaneous volumetric imaging with high spatiotemporal resolution and high dynamic range force capability (10 pN - 100 nN). With this system we have captured lysosome trafficking, vimentin nuclear caging, and actin dynamics on the order of one second per single-cell volume. To showcase the unique advantages of combining Line Bessel light sheet imaging with AFM, we measured the forces exerted by a macrophage during FcɣR-mediated phagocytosis while performing both sequential two-color, fixed plane and volumetric imaging of F-actin. This unique instrument allows for a myriad of novel studies investigating the coupling of cellular dynamics and mechanical forces.

A three-dimensional finite element model of maximal grip loading in the human wrist.

The aim of this work was to create an anatomically accurate three-dimensional finite element model of the wrist, applying subject-specific loading and quantifying the internal load transfer through the joint during maximal grip. For three subjects, representing the anatomical variation at the wrist, loading on each digit was measured during a maximal grip strength test with simultaneous motion capture. The internal metacarpophalangeal joint load was calculated using a biomechanical model. High-resolution magnetic resonance scans were acquired to quantify bone geometry. Finite element analysis was performed, with ligaments and tendons added, to calculate the internal load distribution. It was found that for the maximal grip the thumb carried the highest load, an average of 72.2 +/- 20.1 N in the neutral position. Results from the finite element model suggested that the highest regions of stress were located at the radial aspect of the carpus. Most of the load was transmitted through the radius, 87.5 per cent, as opposed to 12.5 per cent through the ulna with the wrist in a neutral position. A fully three-dimensional finite element analysis of the wrist using subject-specific anatomy and loading conditions was performed. The study emphasizes the importance of modelling a large ensemble of subjects in order to capture the spectrum of the load transfer through the wrist due to anatomical variation.

Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1alpha in rat muscle.

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-cAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferator-activated receptor-gamma coactivator-1alpha, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.

High-resolution 3D isotropic MR imaging of mouse flank tumours obtained in vivo with solenoid RF micro-coil.

The investigation of mouse flank tumours by magnetic resonance imaging (MRI) is limited by the achievable spatial resolution, which is generally limited by the critical problem of signal-to-noise ratio. Sensitivity was improved by using an optimized solenoid RF micro-coil, built into the animal cradle. This simple design did not require extensive RF engineering expertise to construct, yet allowed high-resolution 3D isotropic imaging at 60 x 60 x 60 microm(3) for a flank tumour in vivo, revealing the heterogeneous internal structure of the tumour. It also allowed dynamic contrast enhanced (DCE) experiments and angiography (MRA) to be performed at 100 x 100 x 100 microm(3) resolution. The DCE experiments provided an excellent example of the diffusive spreading of contrast agent into less vascularized tumour tissue. This work is the first step in using high-resolution 3D isotropic MR to study transport in mouse flank tumours.

Atherosclerotic Carotid Plaque Composition: A 3T and 7T MRI-Histology Correlation Study.

BACKGROUND AND PURPOSE: Carotid artery atherosclerotic plaque composition may influence plaque stability and risk of thromboembolic events, and noninvasive plaque imaging may therefore permit risk stratification for clinical management. Plaque composition was compared using noninvasive in vivo (3T) and ex vivo (7T) MRI and histopathological examination. METHODS: Thirty-three endarterectomy cross-sections, from 13 patients, were studied. The data sets consisted of in vivo 3T MRI, ex vivo 7T MRI, and histopathology. Semiautomated segmentation methods were used to measure areas of different plaque components. Bland-Altman plots and mean difference with 95% confidence interval were carried out. RESULTS: There was general quantitative agreement between areas derived from semiautomated segmentation of MRI data and histology measurements. The mean differences and 95% confidence bounds in the relative to total plaque area between 3T versus Histology were: fibrous tissue 4.99%(-4.56 to 14.56), lipid-rich/necrotic core (LR/NC) with hemorrhage -1.81%(-14.11 to 10.48), LR/NC without hemorrhage -2.43%(-13.04 to 8.17), and calcification -3.18%(-11.55 to 5.18). The mean differences and 95% confidence bounds in the relative to total plaque area between 7T and histology were: fibrous tissue 3.17%(-3.17 to 9.52), LR/NC with hemorrhage -0.55%(-9.06 to 7.95), LR/NC without hemorrhage -12.62%(-19.8 to -5.45), and calcification -2.43%(-9.97 to 4.73). CONCLUSIONS: This study provides evidence that semiautomated segmentation of 3T/7T MRI techniques can help to determine atherosclerotic plaque composition. In particular, the high resolution of ex vivo 7T data was able to highlight greater detail in the atherosclerotic plaque composition. High-field MRI may therefore have advantages for in vivo carotid plaque MRI.

Early 1H magnetic resonance spectroscopy of acute head injury: four cases.

In an attempt to examine in vivo the early metabolic consequences of severe acute head injury, 1H MRS was performed in four patients from 8 to 25 h (mean 15 h) following trauma. In three of these patients, decompressive surgery was performed 4-5 h prior to the MRS. High levels of lactate (area of lactate peak >50% of the mean areas of the NAA, choline-containing, and creatine-containing compound peaks) were found at 8 h posttrauma in the one patient who was not operated on and at 10 h posttrauma in one of the patients who underwent surgery. In the other two postoperative patients, at 18 and 25 h after trauma, lactate levels were found to be low (lactate peak <20% of the mean area of the other three peaks). In the one patient who had a follow-up at 6 days and who had the largest initial lactate levels, these remained high. These findings suggest that high levels of lactate may not be an inevitable consequence of severe head injury and that similar MRS studies should be performed on each individual patient before therapies to reduce lactate are considered. There appeared to be no correlation between the relative amounts of lactate and outcome.

Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome.

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.

Ataralgesia in outpatient urology. Clinical evaluation.

The combination of fentanyl citrate (Sublimaze) and diazepam (Valium) was evaluated for efficacy of analgesia, sedation, and safety in 1,008 predominately outpatient urologic procedures. These procedures included prostate biopsies, basket extractions of ureteral calculi, internal urethrotomies, and cystourethroscopies. Ninety-two per cent were judged to be successful with regard to adequate tranquilization and relief of pain. No detrimental effects were seen with the recommmended method and dosage. This drug combination provides the clinician with an effective and safe alternative to local, general, or spinal anesthesia for many routine urologic procedures and allows them to becom true office procedures.

Habituation-like effects cause a significant decrease in response in MRI neuroactivation during visual stimulation.

A wide range of rest/stimulus cycle durations (40-360 sec) is reported to have been used by various groups for MRI neuroactivation studies of the visual cortex. In this paper we demonstrate a clear habituation-like response for longer cycle durations which results in a halving of apparent activation between cycle durations of 138 and 276 sec. This has important implications, not only in terms of optimizing the technique, but also in providing an insight into the underlying physiological mechanisms.

Magnetic resonance imaging of acute subarachnoid hemorrhage.

The feasibility, safety, and diagnostic value of magnetic resonance (MR) imaging versus computerized tomography (CT) scanning were compared in 30 patients with clinical evidence of subarachnoid hemorrhage. Subarachnoid blood was identified more often and more information was available about the site and source of the hemorrhage on MR imaging than on CT. Magnetic resonance imaging could be used safely both before and after the operation, provided that nonferromagnetic clips were used and that comprehensive monitoring and cardiorespiratory support were available. Postoperative studies showed that artifacts from metallic implants and from patient movement caused less image degradation on MR images than on CT scans.

Intracranial deformation caused by brain tumors: assessment of 3-D surface by magnetic resonance imaging.

A shape analysis technique has been developed to quantify intracranial deformation as a means of objectively assessing treatment for brain tumor. Conventional measurements of tumor volume are prone to ambiguity and error, so instead the authors are investigating the secondary space occupying effects of tumor, namely the deformation of structures within the brain. In order to avoid surface segmentation problems in MR images and to facilitate computation, the B-splines method has been introduced to approximate digital 3-D image surfaces. Using the mean curvature and the Gaussian curvature the authors classify a surface into 4 basic types: planar, parabolic, elliptic, and hyperbolic. The deformation of a surface can be described by measuring the geometric changes in these basic types. The method is independent of size, domain (translation), and viewpoint (rotation). These invariance properties are important as they overcome problems caused by wide variations in brain size within the normal population as well as small differences in patient orientation during acquisition. Experimental results show the potential of the technique in objectively monitoring patient response to treatment.

Errors in MR stereotaxy due to undetected extraneous metal objects.

MR stereotaxic procedures are being increasingly used, particularly in functional neurosurgery where very high levels of localization accuracy are required. Whilst many studies have investigated intrinsic causes of non-linearity, potential errors due to an extrinsic cause are not generally appreciated. It is not uncommon to find objects such as hair clips, paper clips and pins inside high-field magnets. They can remain undetected for long periods because they can reach positions not open to visual inspection and because they often do not produce observable deterioration in routine image quality. In this study we measured the maximum absolute positional shifts caused by such objects and found that these can be significant (> 1 mm, even up to 200 mm from one such object). Additional measurements were performed using an MR compatible Leksell stereotaxic frame to calculate actual stereotaxic coordinate errors. The encompassing nature of the frame is such that some degree of compensation for such nonlinearities is inherent, and so errors for areas of the brain more proximal to the object are found to be reduced but not eliminated. Stereotaxic coordinate errors will not be reduced in nonencompassing designs and in frameless stereotaxy. The prevalence of such objects in clinical systems and the measures required to detect their presence are discussed. The need for quality control testing before each stereotaxic procedure is highlighted.

Estimation of torque on mechanical heart valves due to magnetic resonance imaging including an estimation of the significance of the Lenz effect using a computational model.

Mitral and aortic valve replacement is a procedure which is common in cardiac surgery. Some of these replacement valves are mechanical and contain moving metal parts. Should the patient in whom such a valve has been implanted be involved in magnetic resonance imaging, there is a possible dangerous interaction between the moving metal parts and the static magnetic field due to the Lenz effect. Mathematical models of two relatively common forms of single-leaflet valves have been derived and the magnitude of the torque which opposes the motion of the valve leaflet has been calculated for a valve disc of solid metal. In addition, a differential model of a ring-strengthener valve type has been considered to determine the likely significance of the Lenz effect in the context of the human heart. For common magnetic field strengths at present, i.e. 1 to 2 T, the effect is not particularly significant. However, there is a marked increase in back pressure as static magnetic field strength increases. There are concerns that, since field strengths in the range 3 to 4 T are increasingly being used, the Lenz effect could become significant. At 5 to 10 T the malfunction of the mechanical heart valve could cause the heart to behave as though it is diseased. For unhealthy or old patients this could possibly prove fatal.

A physical comparison of two fixed-angle emission tomographic cardiac imaging systems.

Two 7-pinhole tomographic imaging systems for large and small field-of-view gamma cameras were compared with a standard rotating slant-hole system in terms of planar resolution and resolution with depth. Other measurements include the determination of the depths of the reconstructed planes, image miniaturization and scintislice area variation with depth, the effect of scatter on resolution and the variation in resolution across the reconstructed plane. The pinhole sensitivities and the relative reconstructed sensitivities with depth were also measured. The rotating slant-hole system is found to have better depth resolution, a better scatter correction, has more uniform reconstructed sensitivities, is easier to position over the patient but requires significantly longer data acquisition times than the 7-pinhole system.

Method of determination of three dimensional index finger moment arms and tendon lines of action using high resolution MRI scans.

High-resolution MRI scans, in conjunction with CAD software, were used to determine the three-dimensional moment arms and force vector direction cosines for 11 structures passing the interphalangeal and metacarpophalangeal joints of the index finger. The results are presented for five different angles of joint flexion for a single subject. The moment arm data obtained differ from previous studies, where results have been derived from tendon excursion techniques or geometrical models. These dissimilarities have been accounted for by the differences in experimental techniques.

The use of in vitro magnetic resonance tissue studies to optimise pulse sequences in the imaging of intracranial haemorrhage.

The choice of appropriate MR pulse sequences to highlight a particular pathology to best advantage is not always straightforward. In this study of intracranial haemorrhage, tissue relaxation times measured in vitro were entered into a computer program which calculated the signal intensity of each tissue (brain, blood, CSF, and bloody CSF) for all possible echo (TE) and repeat (TR) times. Analysis of graph plots of the results enabled the selection of pulse sequences which gave optimal separation of the signal intensities of intracranial haemorrhage from those of normal intracranial contents. The sequences thus chosen were used successfully in the imaging of patients with intracranial haemorrhage.

Human cranial CSF volumes measured by MRI: sex and age influences.

Accurate measurements of CSF volumes would assist in the diagnosis of several important neurological conditions. Using Magnetic Resonance Imaging (MRI) we have devised a method to measure both total intracranial CSF volume and ventricular volume. This initial study, in normal humans, provides an answer to two longstanding questions: first, do these volumes differ between the sexes; second, do both total and ventricular CSF volumes increase with normal aging? We found that the total cranial CSF volume and skull size of males were significantly greater than those of females, but that there was not a statistically significant difference between the ventricular volumes of the sexes. Total cranial CSF volume increased steeply with age in both sexes but although there was an increase in ventricular volume with age in males, no significant increase with age could be demonstrated in females.