Ultralow-noise Terahertz Detection by p-n Junctions in Gapped Bilayer Graphene.

Graphene shows strong promise for the detection of terahertz (THz) radiation due to its high carrier mobility, compatibility with on-chip waveguides and transistors, and small heat capacitance. At the same time, weak reaction of graphene's physical properties on the detected radiation can be traced down to the absence of a band gap. Here, we study the effect of electrically induced band gap on THz detection in graphene bilayer with split-gate p-n junction. We show that gap induction leads to a simultaneous increase in current and voltage responsivities. At operating temperatures of ∼25 K, the responsivity at a 20 meV band gap is from 3 to 20 times larger than that in the gapless state. The maximum voltage responsivity of our devices at 0.13 THz illumination exceeds 50 kV/W, while the noise equivalent power falls down to 36 fW/Hz1/2.

Terahertz Photoconductivity in Bilayer Graphene Transistors: Evidence for Tunneling at Gate-Induced Junctions.

Photoconductivity of novel materials is the key property of interest for design of photodetectors, optical modulators, and switches. Despite the photoconductivity of most novel 2d materials having been studied both theoretically and experimentally, the same is not true for 2d p-n junctions that are necessary blocks of most electronic devices. Here, we study the sub-terahertz photocoductivity of gapped bilayer graphene with electrically induced p-n junctions. We find a strong positive contribution from junctions to resistance, temperature resistance coefficient, and photoresistivity at cryogenic temperatures T ∼ 20 K. The contribution to these quantities from junctions exceeds strongly the bulk values at uniform channel doping even at small band gaps of ∼10 meV. We further show that positive junction photoresistance is a hallmark of interband tunneling, and not of intraband thermionic conduction. Our results point to the possibility of creating various interband tunneling devices based on bilayer graphene, including steep-switching transistors and selective sensors.

Active and Passive Tuning of Ultranarrow Resonances in Polaritonic Nanoantennas.

Optical nanoantennas are of great importance for photonic devices and spectroscopy due to their capability of squeezing light at the nanoscale and enhancing light-matter interactions. Among them, nanoantennas made of polar crystals supporting phonon polaritons (phononic nanoantennas) exhibit the highest quality factors. This is due to the low optical losses inherent in these materials, which, however, hinder the spectral tuning of the nanoantennas due to their dielectric nature. Here, active and passive tuning of ultranarrow resonances in phononic nanoantennas is realized over a wide spectral range (≈35 cm-1 , being the resonance linewidth ≈9 cm-1 ), monitored by near-field nanoscopy. To do that, the local environment of a single nanoantenna made of hexagonal boron nitride is modified by placing it on different polar substrates, such as quartz and 4H-silicon carbide, or covering it with layers of a high-refractive-index van der Waals crystal (WSe2 ). Importantly, active tuning of the nanoantenna polaritonic resonances is demonstrated by placing it on top of a gated graphene monolayer in which the Fermi energy is varied. This work presents the realization of tunable polaritonic nanoantennas with ultranarrow resonances, which can find applications in active nanooptics and (bio)sensing.

Multiple sensory illusions are evoked during the course of proton therapy.

Visual illusions from astronauts in space have been reported to be associated with the passage of high energy charged particles through visual structures (retina, optic nerve, brain). Similar effects have also been reported by patients under proton and heavy ion therapies. This prompted us to investigate whether protons at the Loma Linda University Proton Therapy and Research Center (PTRC) may also affect other sensory systems beside evoking similar perceptions on the visual system. A retrospective review of proton radiotherapy patient records at PTRC identified 29 sensory reports from 19 patients who spontaneously reported visual, olfactory, auditory and gustatory illusions during treatment. Our results suggest that protons can evoke neuronal responses sufficient to elicit conscious sensory illusion experiences, in four senses (auditory, taste, smell, and visual) analogous to those from normal sensory inputs. The regions of the brain receiving the highest doses corresponded with the anatomical structures associated with each type of illusion. Our findings suggest that more detailed queries about sensory illusions during proton therapy are warranted, possibly integrated with quantitative effect descriptions (such as electroencephalography) and can provide additional physiological basis for understanding the effects of protons on central nervous system tissues, needed for radiation risk assessment in advance of deep space human exploration.

Comparison of procalcitonin, C-reactive protein, white blood cell count and clinical status in diagnosing pneumonia in patients hospitalized with acute exacerbations of COPD: A prospective observational study.

Lower respiratory tract infection is the most common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of the present study was to compare the accuracy of procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) as single diagnostic tests and in combination with clinical signs and symptoms to diagnose pneumonia in patients hospitalized with AECOPD. This was a prospective, single centre observational study. Patients with spirometry-confirmed COPD who were hospitalized due to AECOPD were consecutively recruited at the hospital's Emergency Unit. Pneumonia was defined as a new pulmonary infiltrate on chest X-ray. The values of PCT, CRP and WBC were determined at admission. Receiver operating characteristic (ROC) curve analysis was used to study the accuracy of various diagnostic tests. Of the 113 included patients, 35 (31%) had pneumonia at admission. Area under the ROC curve (AUC) for PCT, CRP and WBC as a single test to distinguish between patients with and without pneumonia was 0.67 (95% CI 0.55-0.79), 0.73 (95% CI 0.63-0.84) and 0.67 (95% CI 0.55-0.79), respectively ( p = 0.42 for the test of difference). The AUC for a model of clinical signs and symptoms was 0.84 (95% CI 0.76-0.92). When biomarkers were added to the clinical model, the AUCs of the combined models were not significantly different from that of the clinical model alone ( p = 0.54). PCT had about the same accuracy as CRP and WBC in predicting pneumonia in patients hospitalized with AECOPD both as a single test and in combination with clinical signs and symptoms.

Does an Integrated Care Intervention for COPD Patients Have Long-Term Effects on Quality of Life and Patient Activation? A Prospective, Open, Controlled Single-Center Intervention Study.

BACKGROUND: Implementation of the COPD-Home integrated disease management (IDM) intervention at discharge after hospitalizations for acute exacerbations of COPD (AECOPD) led to reduced hospital utilization during the following 24 months compared to the year prior to study start. AIMS: To analyze the impact of the COPD-Home IDM intervention on health related quality of life, symptoms of anxiety and depression, and the degree of patient activation during 24 months of follow-up and to assess the association between these outcomes. METHODS: A single center, prospective, open, controlled clinical study. Changes in The St. George Respiratory Questionnaire (SGRQ), the Hospital anxiety (HADS-A) and depression (HADS-D) and the patient activation measure (PAM) scores were compared between the patients in the integrated care group (ICG) and the usual care group (UCG) 6, 12 and 24 months after enrolment. RESULTS: The questionnaire response rate was 80-96%. There were no statistically significant differences in the change of the SGRQ scores between the groups during follow up. After 12 months of follow-up there was a trend towards a reduction in the mean HADS-A score in the ICG compared to the UCG. The HADS-D scores remained stable in the ICG compared with an increasing trend in the UCG. Clinically significant difference in the PAM score was achieved only in the ICG, 6.7 (CI95% 0.7 to 7.5) compared to 3.6 (CI95% -1.4 to 8.6) in the UCG. In a logistic regression model a higher HADS-D score and current smoking significantly increased the odds for a low PAM score. CONCLUSION: The COPD-Home IDM intervention did not result in any statistically significant changes in mean SGRQ, HADS-A, HADS- D or PAM scores during the 24 months of follow-up. TRIAL REGISTRATION: The ID number for the study in the Clinical.Trials.gov registration system is 17417. ClinicalTrials.gov Identifier: NCT 00702078.

Neutrophil CD64 Expression as a Diagnostic Marker in Patients Hospitalized with Exacerbations of COPD: A Prospective Observational Study.

PURPOSE: The expression of the neutrophil high-affinity Fc-gamma receptor (CD64) can be used as a diagnostic marker for bacterial infection and sepsis. The aims of this study were to determine the diagnostic accuracy of CD64 compared to C-reactive protein (CRP) and white blood cell count (WBC) in patients hospitalized with acute exacerbations of COPD (AECOPD) and to investigate the kinetics of CD64 expression. METHODS: The present study is a prospective, single-centre observation study. Blood samples were collected from patients hospitalized with AECOPD at admission and after 6, 24 and 48 h. Retrospective reviews on the patients' medical records were performed blinded to the CD64 results. The CD64 was measured using the Leuko64 kit from Trillium Diagnostics, LLC (Maine, USA) with the CELL-DYN Sapphire Haematology System (Abbott Laboratories, Illinois, USA). Diagnostic accuracy of the CD64, CRP and WBC was compared using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 113 patients were included. Thirty-six patients (32 %) had pulmonary infiltrate on chest X-ray at admission (PI). The CD64 was higher in samples from patients with AECOPD and PI than those without PI at admission (median 1.25 vs. 0.60, p = 0.002) and during 48 h of follow-up. The area under the ROC curve of CD64, CRP and WBC was 0.69, 0.73 and 0.64, respectively, (p = 0.42 for the test of difference). CONCLUSION: Neutrophil CD64 expression has about the same diagnostic accuracy as CRP in diagnosing pneumonia in patients hospitalized with AECOPD, but does not add to the diagnostic accuracy of CRP and WBC count.

Long term effects of an integrated care intervention on hospital utilization in patients with severe COPD: a single centre controlled study.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality globally. In Trondheim in 2008 an integrated care model (COPD-Home) consisting of an education program, self-management plan, home visits and a call centre for patient support and communication was developed. The objective was to determine the efficacy of an intervention according to the COPD-Home model in reducing hospital utilization among patients with COPD stage III and IV (GOLD 2007) discharged after hospitalization for acute exacerbations of COPD (AECOPD). METHODS: A single centre, prospective, open, controlled clinical study comparing COPD-Home integrated care (IC) with usual care (UC). RESULTS: Ninety-one versus 81 patients mean age 73.4 ± 9.3 years (57% women) were included in the IC group (ICG) and the UC group (UCG) respectively, and after 2 years 51 and 49 patients were available for control in the respective groups. During the year prior to study start there were 71 hospital admissions (HA) in the ICG and 84 in the UCG. There was a 12.6% reduction in HA in the ICG during the first year of follow-up and a 46.5% reduction during the second year (p = 0.01) compared to an 8.3% increase during the first year and no change during the second year in the ICG. During the year prior to study start, the number of hospital days (HD) was 468 in the ICG and 479 in the UCG. In the IC group, the number of HD was reduced by 48.3% during the first year (p = 0.01), and remained low during the second year of follow-up (p=0.02). In the UC group, the number of HD remained unchanged during the follow-up period. There was a trend towards a shorter survival time among patients in the ICG compared to the UCG, hazard ratio 1.33 [95% CI 0.77 to 2.33]. CONCLUSION: Intervention according to the COPD-Home model reduced hospital utilization in patients with COPD III and IV with a persisting effect throughout the 2 years of follow-up. However, there was a trend towards a shorter survival time in the intervention group.

Brain irradiation improves focal cerebral ischemia recovery in aged rats.

BACKGROUND: Studies have shown that aging is a significant factor in worsening stroke outcomes. While many mechanisms may aggravate brain injury in the elderly, one such potential system may involve increased glial proliferation in the aged stroke patient that could result in increased scar formation. We hypothesized that in aged rats a single brain-only exposure to a low radiation dose prior to focal brain ischemia would reduce glial proliferation and confer a long-term neuroprotective effect. METHODS: Brain-only proton irradiation (8 Gy) was performed ten days prior to middle cerebral artery occlusion (MCAO) in aged male rats. Magnetic resonance imaging (MRI) was undertaken in naive, radiation-only (Rad), MCAO, and MCAO+Rad groups at 2, 14 and 28 days post-stroke followed by immunohistochemistry (day 28). RESULTS: Ischemic lesion volume in MCAO+Rad group was decreased by 50.7% with an accelerated temporal reduction in peri-lesional brain edema and increased water mobility within the ischemic core (39.8%) compared to MCAO-only rats. In the peri-lesional brain region of MCAO+Rad rats there was a decreased scar formation (49%, glial fibrillary acidic protein), brain tissue sclerosis (30%, aquaporin-4) and necrosis/apoptosis (58%, TUNEL positive cells) compared to those in MCAO animals. CONCLUSION: In aged animals a single exposure to brain-only radiation prior to focal cerebral ischemia is neuroprotective as it prevents glial hyperproliferation, progressive brain tissue sclerosis and reduces the apoptosis/necrosis in the peri-lesional region. Decreased lesion volume is in agreement with accelerated reduction of brain edema in these animals.

The effects of tetrahydrobiopterin on intracerebral hemorrhage-induced brain injury in mice.

Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and is presently used clinically to treat forms of phenylketonuria. BH4 has been reported to restrain superoxide generation of NOS and chemically reduce superoxide. However, there has been no report concerning the effects of BH4 in intracerebral hemorrhage (ICH). In the present study, we investigated the neuroprotective effect of BH4 against ICH-induced brain injury in a mouse model.A total of 26 male CD1 mice (31-39 g) were divided into sham, ICH-vehicle, and ICH-treated with BH4 groups (n = 8 in each group). ICH was induced by collagenase injection into the right basal ganglia. BH4 (20 mg/kg) was administrated intraperitoneally at 1 h after ICH. The effect of BH4 was measured by neurological score and brain water content at 24 h after ICH.Our data demonstrates that ICH caused significant neurological deficit that is associated with brain edema. Treatment with BH4 did not reduce brain edema and neurological deficits at 24 h after ICH in mice. Further study is required to investigate the long-term effect of BH4 in ICH-induced brain injury.

Experimental models of subarachnoid hemorrhage for studies of cerebral vasospasm.

OBJECTIVE: A multitude of subarachnoid hemorrhage (SAH) models have been described but only several of them are still in use. All models to a different degree helped in understanding of pathophysiology of cerebral vasospasm after SAH. Their advantages and drawbacks have been reviewed in this paper. Since 2000, when the last review on cerebral vasospasm in animal models was written, new animal models of SAH were introduced and our knowledge about pathophysiology of CVS improved. The aim of present review was to update the information about well established and newly implemented models of vasospasm after SAH. MATERIALS AND METHODS: The MEDLINE searches were carried out using keywords that included 'subarachnoid hemorrhage', 'animal', 'model', as well as names of animal species such as 'rats', 'dogs', 'mice', 'rabbits', 'pigs' or animal groups, e.g. 'non-human primates'. Owing to a limited volume, only models of SAH in vivo were included in our review. RESULTS: We identified 53 original models of SAH in considered groups of animals. For the past several years, use of rats and mice became increasingly common in vasospasm studies due to advancements of imaging techniques, new approaches in vessel morphometry and reduced costs related to small animals. However, dog model of SAH is still considered superior for vasospasm studies as the ability of murine models to model human vasospasm is disputed. CONCLUSION: Testing new concepts of vasospasm etiology will require re-evaluation of in vivo models of CVS. The updated knowledge about their advantages and limitations is necessary for effective design in future studies of cerebral vasospasm after SAH.

Reduced brain injury in CD18-deficient mice after experimental intracerebral hemorrhage.

Many studies have indicated leukocytes are a major contributor to brain injuries caused by intracerebral hemorrhage (ICH). Leukocyte-expressed CD18 is important for neutrophil-endothelial interactions in the vasculature, and CD18 deficiency protects against ischemia-reperfusion injury. We investigated whether CD18 deficiency provides protection against ICH-induced brain injury. Male wild-type (WT) CD18(+/+) mice and CD18(-/-) -knockout mice were used in this study. ICH was induced by a collagenase injection. Mortality, neurological function, brain edema, and myeloperoxidase (MPO) activity as well as tissue expression of nitrotyrosine and MPO were evaluated 24 hr after ICH. We discovered significantly reduced brain edema and diminished mortality with a concomitant decrease in MPO and nitrotyrosine immunoreactivity in brains of CD18-knockout mice.

The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia.

We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.

Oxidative stress after subarachnoid hemorrhage in gp91phox knockout mice.

BACKGROUND: Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH. METHODS: Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery. RESULTS: Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice. CONCLUSIONS: Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.

Effects of apocynin and ethanol on intracerebral haemorrhage-induced brain injury in rats.

1. In the present study, we investigated whether the administration of apocynin, an NADPH oxidase inhibitor, provided brain protection in a rat model of intracerebral haemorrhage (ICH). 2. Rats were divided into sham, ICH untreated, ICH treated with vehicle (ethanol) and ICH treated with apocynin groups. Intracerebral haemorrhage was induced by collagenase injection. Neurological function, haemorrhage volume and brain oedema were measured 24 h after ICH. 3. Intracerebral haemorrhage caused significant neurological deficit associated with brain oedema. Apocynin (3, 10 and 30 mg/kg) failed to reduce brain injury after ICH. Low dose ethanol (0.2 g/kg) improved neurological function and reduced brain oedema (ICH-vehicle vs ICH-untreated, P < 0.05). 4. In conclusion, apocynin has no neuroprotective effect when administered intraperitoneally after ICH.

NADPH oxidase inhibition improves neurological outcomes in surgically-induced brain injury.

Neurosurgical procedures can result in brain injury by various means including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause post-operative complications such as brain edema. By creating a mouse model of SBI, we tested whether NADPH oxidase, an important reactive oxygen species producing enzyme, is involved in SBI using transgenic mice lacking gp91phox subunit of NADPH oxidase (gp91phox KO) and apocynin, a specific inhibitor of NADPH oxidase. Neurological function and brain edema were evaluated at 24 h post-SBI in gp91phox KO and wild-type littermates grouped into SBI and sham-surgery groups. Alternatively, mice were grouped into vehicle- and apocynin-treated (5 mg/kg, i.p. 30 min before SBI) groups. Oxidative stress indicated by lipid peroxidation (LPO) was measured at 3 and 24 h post-SBI. The gp91phox KO mice, but not the apocynin-treated mice showed significantly improved neurological scores. Brain edema was observed in both gp91phox KO and wild-type groups after SBI; however, there was no significant difference between these two groups. Brain edema was also not affected by apocynin-pretreatment. LPO levels were significantly higher in SBI group in both gp91phox KO and wild-type groups as compared to sham group. A trend, although without statistical significance, was noted towards attenuation of LPO in the gp91phox KO animals as compared to wild-type group. LPO levels were significantly attenuated at 3 h post-SBI by apocynin-pretreatment but not at 24 h post-SBI. These results suggest that chronic and acute inhibition of NADPH oxidase activity does not reduce brain edema after SBI. Long-term inhibition of NADPH oxidase, however improves neurological functions after SBI.

A plant caspase-like protease activated during the hypersensitive response.

To test the hypothesis that caspase-like proteases exist and are critically involved in the implementation of programmed cell death (PCD) in plants, a search was undertaken for plant caspases activated during the N gene-mediated hypersensitive response (HR; a form of pathogen-induced PCD in plants) in tobacco plants infected with Tobacco mosaic virus (TMV). For detection, characterization, and partial purification of a tobacco caspase, the Agrobacterium tumefaciens VirD2 protein, shown here to be cleaved specifically at two sites (TATD and GEQD) by human caspase-3, was used as a target. In tobacco leaves, specific proteolytic processing of the ectopically produced VirD2 derivatives at these sites was found to occur early in the course of the HR triggered by TMV. A proteolytic activity capable of specifically cleaving the model substrate at TATD was partially purified from these leaves. A tetrapeptide aldehyde designed and synthesized on the basis of the elucidated plant caspase cleavage site prevented fragmentation of the substrate protein by plant and human caspases in vitro and counteracted TMV-triggered HR in vivo. Therefore, our data provide a characterization of caspase-specific protein fragmentation in apoptotic plant cells, with implications for the importance of such activity in the implementation of plant PCD.