Measurement of the 187Re({\alpha},n)190Ir reaction cross section at sub-Coulomb energies using the Cologne Clover Counting Setup

Uncertainties in adopted models of particle+nucleus optical-model potentials directly influence the accuracy in the theoretical predictions of reaction rates as they are needed for reaction-network calculations in, for instance, {\gamma}-process nucleosynthesis. The improvement of the {\alpha}+nucleus optical-model potential is hampered by the lack of experimental data at astrophysically relevant energies especially for heavier nuclei. Measuring the Re187({\alpha},n)Ir190 reaction cross section at sub-Coulomb energies extends the scarce experimental data available in this mass region and helps understanding the energy dependence of the imaginary part of the {\alpha}+nucleus optical-model potential at low energies. Applying the activation method, after the irradiation of natural rhenium targets with {\alpha}-particle energies of 12.4 to 14.1 MeV, the reaction yield and thus the reaction cross section were determined via {\gamma}-ray spectroscopy by using the Cologne Clover Counting Setup and the method of {\gamma}{\gamma} coincidences. Cross-section values at five energies close to the astrophysically relevant energy region were measured. Statistical model calculations revealed discrepancies between the experimental values and predictions based on widely used {\alpha}+nucleus optical-model potentials. However, an excellent reproduction of the measured cross-section values could be achieved from calculations based on the so-called Sauerwein-Rauscher {\alpha}+nucleus optical-model potential. The results obtained indicate that the energy dependence of the imaginary part of the {\alpha}+nucleus optical-model potential can be described by an exponential decrease. Successful reproductions of measured cross sections at low energies for {\alpha}-induced reactions in the mass range 141{\leq}A{\leq}187 confirm the global character of the Sauerwein-Rauscher potential

Red Team vs. Blue Team: A Real-World Hardware Trojan Detection Case Study Across Four Modern CMOS Technology Generations

Verifying the absence of maliciously inserted Trojans in ICs is a crucial task – especially for security-enabled products. Depending on the concrete threat model, different techniques can be applied for this purpose. Assuming that the original IC layout is benign and free of backdoors, the primary security threats are usually identified as the outsourced manufacturing and transportation. To ensure the absence of Trojans in commissioned chips, one straightforward solution is to compare the received semiconductor devices to the design files that were initially submitted to the foundry. Clearly, conducting such a comparison requires advanced laboratory equipment and qualified experts. Nevertheless, the fundamental techniques to detect Trojans which require evident changes to the silicon layout are nowadays well-understood. Despite this, there is a glaring lack of public case studies describing the process in its entirety while making the underlying datasets publicly available. In this work, we aim to improve upon this state of the art by presenting a public and open hardware Trojan detection case study based on four different digital ICs using a Red Team vs. Blue Team approach. Hereby, the Red Team creates small changes acting as surrogates for inserted Trojans in the layouts of 90 nm, 65 nm, 40 nm, and 28 nm ICs. The quest of the Blue Team is to detect all differences between digital layout and manufactured device by means of a GDSII–vs–SEM-image comparison. Can the Blue Team perform this task efficiently? Our results spark optimism for the Trojan seekers and answer common questions about the efficiency of such techniques for relevant IC sizes. Further, they allow to draw conclusions about the impact of technology scaling on the detection performance

Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies

Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation—evading the systemic therapy—in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke

Determination of 141Pr(alpha,n)144Pm cross sections at energies of relevance for the astrophysical p-process using the gamma-gamma coincidence method

The reaction 141Pr(alpha,n)144Pm was investigated between E_alpha=11 MeV and 15 MeV with the activation method using the gamma-gamma coincidence method with a segmented clover-type high-purity Germanium (HPGe) detector. Measurements with four other HPGe detectors were additionally made. The comparison proves that the gamma-gamma coincidence method is an excellent tool to investigate cross sections down to the microbarn range. The (alpha,n) reaction at low energy is especially suited to test alpha+nucleus optical-model potentials for application in the astrophysical p-process. The experimentally determined cross sections were compared to Hauser-Feshbach statistical model calculations using different optical potentials and generally an unsatisfactory reproduction of the data was found. A local potential was constructed to improve the description of the data. The consequences of applying the same potential to calculate astrophysical (gamma,alpha) rates for 145Pm and 148Gd were explored. In summary, the data and further results underline the problems in global predictions of alpha+nucleus optical potentials at astrophysically relevant energies.Comment: 13 pages, 9 figures, accepted in Phys. Rev.

Indirect readout: detection of optimized subsequences and calculation of relative binding affinities using different DNA elastic potentials

Essential biological processes require that proteins bind to a set of specific DNA sites with tuned relative affinities. We focus on the indirect readout mechanism and discuss its theoretical description in relation to the present understanding of DNA elasticity on the rigid base pair level. Combining existing parametrizations of elastic potentials for DNA, we derive elastic free energies directly related to competitive binding experiments, and propose a computationally inexpensive local marker for elastically optimized subsequences in protein–DNA co-crystals. We test our approach in an application to the bacteriophage 434 repressor. In agreement with known results we find that indirect readout dominates at the central, non-contacted bases of the binding site. Elastic optimization involves all deformation modes and is mainly due to the adapted equilibrium structure of the operator, while sequence-dependent elasticity plays a minor role. These qualitative observations are robust with respect to current parametrization uncertainties. Predictions for relative affinities mediated by indirect readout depend sensitively on the chosen parametrization. Their quantitative comparison with experimental data allows for a critical evaluation of DNA elastic potentials and of the correspondence between crystal and solution structures. The software written for the presented analysis is included as Supplementary Data

Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?

Background: Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Materials and methods: Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Results: Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng m

Efficacy-based perspective to overcome reduced opioid analgesia of advanced painful diabetic neuropathy in rats

Reduction of the opioid analgesia in diabetic neuropathic pain (DNP) results from mu-opioid receptor (MOR) reserve reduction. Herein, we examined the antinociceptive and antiallodynic actions of a novel opioid agonist 14-O-methymorphine-6-O-sulfate (14-O-MeM6SU), fentanyl and morphine in rats with streptozocin-evoked DNP of 9-12 weeks following their systemic administration. The antinociceptive dose-response curve of morphine but not of 14-O-MeM6SU or fentanyl showed a significant right-shift in diabetic compared to non-diabetic rats. Only 14-O-MeM6SU produced antiallodynic effects in doses matching antinociceptive doses obtained in non-diabetic rats. Co-administered naloxone methiodide (NAL-M), a peripherally acting opioid receptor antagonist failed to alter the antiallodynic effect of test compounds, indicating the contribution of central opioid receptors. Reduction in spinal MOR binding sites and loss in MOR immunoreactivity of nerve terminals in the spinal cord and dorsal root ganglia in diabetic rats were observed. G-protein coupling assay revealed low efficacy character for morphine and high efficacy character for 14-O-MeM6SU or fentanyl at spinal or supraspinal levels (E-max values). Furthermore, at the spinal level only 14-O-MeM6SU showed equal efficacy in G-protein activation in tissues of diabetic- and non-diabetic animals. Altogether, the reduction of spinal opioid receptors concomitant with reduced analgesic effect of morphine may be circumvented by using high efficacy opioids, which provide superior analgesia over morphine. In conclusion, the reduction in the analgesic action of opioids in DNP might be a consequence of MOR reduction, particularly in the spinal cord. Therefore, developing opioids of high efficacy might provide analgesia exceeding that of currently available opioids

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6–7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures

K+ Channel Regulator KCR1 Suppresses Heart Rhythm by Modulating the Pacemaker Current If

Hyperpolarization-activated, cyclic nucleotide sensitive (HCN) channels underlie the pacemaker current If, which plays an essential role in spontaneous cardiac activity. HCN channel subunits (HCN1-4) are believed to be modulated by additional regulatory proteins, which still have to be identified. Using biochemistry, molecularbiology and electrophysiology methods we demonstrate a protein-protein interaction between HCN2 and the K+ channel regulator protein 1, named KCR1. In coimmunoprecipitation experiments we show that KCR1 and HCN2 proteins are able to associate. Heterologously expressed HCN2 whole-cell current density was significantly decreased by KCR1. KCR1 profoundly suppressed IHCN2 single-channel activity, indicating a functional interaction between KCR1 and the HCN2 channel subunit. Endogenous KCR1 expression could be detected in adult and neonatal rat ventriculocytes. Adenoviral-mediated overexpression of KCR1 in rat cardiomyocytes (i) reduced If whole-cell currents, (ii) suppressed most single-channel gating parameters, (iii) altered the activation kinetics, (iv) suppressed spontaneous action potential activity, and (v) the beating rate. More importantly, siRNA-based knock-down of endogenous KCR1 increased the native If current size and single-channel activity and accelerated spontaneous beating rate, supporting an inhibitory action of endogenous KCR1 on native If. Our observations demonstrate for the first time that KCR1 modulates IHCN2/If channel gating and indicate that KCR1 serves as a regulator of cardiac automaticity