Detection of Human Ig G Using Photoluminescent Porous Silicon Interferometer.

Photoluminescent porous silicon (PSi) interferometers having dual optical properties, both Fabry-Pérot fringe and photolumincence (PL), have been developed and used as biosensors for detection of Human Immunoglobin G (Ig G). PSi samples were prepared by electrochemical etching of p-type silicon under white light exposure. The surface of PSi was characterized using a cold field emission scanning electron microscope. The sensor system studied consisted of a single layer of porous silicon modified with Protein A. The system was probed with various fragments of aqueous human immunoglobin G (Ig G) analyte. Both reflectivity and PL were simultaneously measured under the exposure of human Ig G. An increase of optical thickness and decrease of PL were obtained under the exposure of human Ig G. Detection limit of 500 fM was observed for the human Ig G.

Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles.

RATIONALE: Stroke is the third most common cause of death in industrialized countries. The main therapeutic target is the ischemic penumbra, potentially salvageable brain tissue that dies within the first few hours after blood flow cessation. Hence, strategies to keep the penumbra alive until reperfusion occurs are needed. OBJECTIVE: To study the effect of inhaled nitric oxide on cerebral vessels and cerebral perfusion under physiological conditions and in different models of cerebral ischemia. METHODS AND RESULTS: This experimental study demonstrates that inhaled nitric oxide (applied in 30% oxygen/70% air mixture) leads to the formation of nitric oxide carriers in blood that distribute throughout the body. This was ascertained by in vivo microscopy in adult mice. Although under normal conditions inhaled nitric oxide does not affect cerebral blood flow, after experimental cerebral ischemia induced by transient middle cerebral artery occlusion it selectively dilates arterioles in the ischemic penumbra, thereby increasing collateral blood flow and significantly reducing ischemic brain damage. This translates into significantly improved neurological outcome. These findings were validated in independent laboratories using two different mouse models of cerebral ischemia and in a clinically relevant large animal model of stroke. CONCLUSIONS: Inhaled nitric oxide thus may provide a completely novel strategy to improve penumbral blood flow and neuronal survival in stroke or other ischemic conditions.

In vivo temporal and spatial profile of leukocyte adhesion and migration after experimental traumatic brain injury in mice.

BACKGROUND: Leukocytes are believed to be involved in delayed cell death following traumatic brain injury (TBI). However, data demonstrating that blood-borne inflammatory cells are present in the injured brain prior to the onset of secondary brain damage have been inconclusive. We therefore investigated both the interaction between leukocytes and the cerebrovascular endothelium using in vivo imaging and the accumulation of leukocytes in the penumbra following experimentally induced TBI. METHODS: Experimental TBI was induced in C57/Bl6 mice (n = 42) using the controlled cortical impact (CCI) injury model, and leukocyte-endothelium interactions (LEI) were quantified using both intravital fluorescence microscopy (IVM) of superficial vessels and 2-photon microscopy of cortical vessels for up to 14 h post-CCI. In a separate experimental group, leukocyte accumulation and secondary lesion expansion were analyzed in mice that were sacrificed 15 min, 2, 6, 12, 24, or 48 h after CCI (n = 48). Finally, leukocyte adhesion was blocked with anti-CD18 antibodies, and the effects on LEI and secondary lesion expansion were determined 16 (n = 12) and 24 h (n = 21), respectively, following TBI. RESULTS: One hour after TBI leukocytes and leukocyte-platelet aggregates started to roll on the endothelium of pial venules, whereas no significant LEI were observed in pial arterioles or in sham-operated mice. With a delay of >4 h, leukocytes and aggregates did also firmly adhere to the venular endothelium. In deep cortical vessels (250 µm) LEIs were much less pronounced. Transmigration of leukocytes into the brain parenchyma only became significant after the tissue became necrotic. Treatment with anti-CD18 antibodies reduced adhesion by 65%; however, this treatment had no effect on secondary lesion expansion. CONCLUSIONS: LEI occurred primarily in pial venules, whereas little or no LEI occurred in arterioles or deep cortical vessels. Inhibiting LEI did not affect secondary lesion expansion. Importantly, the majority of migrating leukocytes entered the injured brain parenchyma only after the tissue became necrotic. Our results therefore suggest that neither intravascular leukocyte adhesion nor the migration of leukocytes into cerebral tissue play a significant role in the development of secondary lesion expansion following TBI.

Adhesion of Leukocytes to Cerebral Venules Precedes Neuronal Cell Death and Is Sufficient to Trigger Tissue Damage After Cerebral Ischemia.

BACKGROUND: Leukocytes contribute to tissue damage after cerebral ischemia; however, the mechanisms underlying this process are still unclear. This study investigates the temporal and spatial relationship between vascular leukocyte recruitment and tissue damage and aims to uncover which step of the leukocyte recruitment cascade is involved in ischemic brain injury. METHODS: Male wild-type, ICAM-1-deficient, anti-CD18 antibody treated, or selectin-deficient [fucusyltransferase (FucT IV/VII-/-)] mice were subjected to 60 min of middle cerebral artery occlusion (MCAo). The interaction between leukocytes and the cerebrovascular endothelium was quantified by in vivo fluorescence microscopy up to 15 h thereafter. Temporal dynamics of neuronal cell death and leukocyte migration were assessed at the same time points and in the same tissue volume by histology. RESULTS: In wild-type mice, leukocytes started to firmly adhere to the wall of pial postcapillary venules two hours after reperfusion. Three hours later, neuronal loss started and 13 h later, leukocytes transmigrated into brain tissue. Loss of selectin function did not influence this process. Application of an anti-CD18 antibody or genetic deletion of ICAM-1, however, significantly reduced tight adhesion of leukocytes to the cerebrovascular endothelium (-60%; p < 0.01) and increased the number of viable neurons in the ischemic penumbra by 5-fold (p < 0.01); the number of intraparenchymal leukocytes was not affected. CONCLUSIONS: Our findings suggest that ischemia triggers only a transient adhesion of leukocytes to the venous endothelium and that inhibition of this process is sufficient to partly prevent ischemic tissue damage.

First-principles study of the ternary effects on the plasticity of [Formula: see text]-TiAl crystals.

We studied the effects of important ternary elements, such as Cr, Nb, and V, on the plasticity of [Formula: see text]-TiAl crystals by calculating the point defect formation energy and the change in the generalized stacking fault energy (GSFE) surface from first-principles calculations. For all three elements, the point defect formation energies of the substitutional defects are lower in the Ti site than in the Al site, which implies that substitution on the Ti site is energetically more stable. We computed the GSFE surfaces with and without a substitutional solute and obtained the ideal critical resolved shear stress (ICRSS) of each partial slip. The change in the GSFE surface indicates that the substitution of Ti with Cr, Nb, or V results in an increase in the yield strength because the ICRSS of the superlattice intrinsic stacking fault (SISF) partial slip increases. Interestingly, we find that Cr substitution on an Al site could occur owing to the small difference between the substitutional defect formation energies of the Ti and Al sites. In that case, the reduction of ICRSSs of the SISF partial slip and twinning would lead to improved twinnability. We discuss the implications of the computational predictions by comparing them with experimental results in the literature.

Systematic investigation of the deformation mechanisms of a γ-TiAl single crystal.

We propose a theoretical framework to predict the deformation mechanism of the γ-TiAl single crystal without lattice defects by combining the generalized stacking fault energy and the Schmid factor. Our theory is validated against an excellent testbed, the single crystal nanowire, by correctly predicting four major deformation mechanisms, namely, ordinary slip, super slip, twinning, and mixed slip/fracture observed during the tensile and compressive tests along 10 different orientations using molecular dynamics simulations. Interestingly, although lattice defects are not taken into account, the theoretical predictions match well with existing experiments on bulk specimen with only a few exceptions; the exceptions are discussed based on the size-dependent deformation mechanism in the presence of preexisting dislocation sources. We expect that the method in this paper can be generalized to study various ductile intermetallic crystals where conventional Schmid law does not hold well.

Nanotransplantation Printing of Crystallographic-Orientation-Controlled Single-Crystalline Nanowire Arrays on Diverse Surfaces.

The fabrication of a highly ordered array of single-crystalline nanostructures prepared from solution-phase or vapor-phase synthesis methods is extremely challenging due to multiple difficulties of spatial arrangement and control of crystallographic orientation. Herein, we introduce a nanotransplantation printing (NTPP) technique for the reliable fabrication, transfer, and arrangement of single-crystalline Si nanowires (NWs) on diverse substrates. NTPP entails (1) formation of nanoscale etch mask patterns on conventional low-cost Si via nanotransfer printing, (2) two-step combinatorial plasma etching for defining Si NWs, and (3) detachment and transfer of the NWs onto various receiver substrates using an infiltration-type polymeric transfer medium and a solvent-assisted adhesion switching mechanism. Using this approach, high-quality, highly ordered Si NWs can be formed on almost any type of surface including flexible plastic substrates, biological surfaces, and deep-trench structures. Moreover, NTPP provides controllability of the crystallographic orientation of NWs, which is confirmed by the successful generation of (100)- and (110)-oriented Si NWs with different properties. The outstanding electrical properties of the NWs were confirmed by fabricating and characterizing Schottky junction field-effect transistors. Furthermore, exploiting the highly flexible nature of the NWs, a high-performance piezoresistive strain sensor, with a high gauge factor over 200 was realized.

Effect of early and delayed decompressive craniectomy on secondary brain damage after controlled cortical impact in mice.

The timing of decompressive craniectomy for the treatment of increased intracranial pressure (ICP) after traumatic brain injury (TBI) is a widely discussed clinical issue. Although we showed recently that early decompression is beneficial following experimental TBI, it remains unclear to what degree decompression craniectomy reduces secondary brain damage and if craniectomy is still beneficial when it is delayed by several hours as often inevitable during daily clinical practice. The aim of the current study was therefore to investigate the influence of craniectomy on secondary contusion expansion and brain edema formation and to determine the therapeutic window of craniectomy. Male C57/Bl6 mice were subjected to controlled cortical impact injury. Contusion volume, brain edema formation, and opening of the blood-brain barrier were investigated 2, 6, 12, and 24 h and 7 days after trauma. The effect of decompression craniectomy on secondary brain damage was studied in control mice (closed skull) and in animals craniotomized immediately or with a delay of 1, 3, or 8 h after trauma. Twenty-four hours after trauma, the time point of maximal lesion expansion (+60% vs. 15 min after trauma) and brain edema formation (+3.0% water content vs. sham), contusion volume in craniotomized mice did not show any secondary expansion; that is, contusion volume was similar to that observed in mice sacrificed immediately after trauma (18.3 +/- 5.3 vs. 22.2 +/- 1.4 mm(3)). Furthermore, brain edema formation was reduced by 52% in craniotomized animals. The beneficial effect of craniectomy was still present even when treatment was delayed by up to 3 h after trauma (p < 0.05). The current study clearly demonstrates that early craniectomy prevents secondary brain damage and significantly reduces brain edema formation after experimental TBI. Evaluation of early craniectomy as a therapeutic option after TBI in humans may therefore be indicated.

Release of bradykinin and expression of kinin B2 receptors in the brain: role for cell death and brain edema formation after focal cerebral ischemia in mice.

Pharmacological studies using bradykinin B2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B2 receptors for brain damage after experimental stroke have not been elucidated so far. C57/Bl6 mice were subjected to 45 mins of middle cerebral artery occlusion (MCAO) and 2, 4, 8, 24, and 48 h later brains were removed for the analysis of tissue bradykinin concentration and kinin B2 receptor mRNA and protein expression. Brain edema, infarct volume, functional outcome, and long-term survival were assessed in WT and B2-/- mice 24 h or 7 days after MCAO. Tissue bradykinin was maximally increased 12 h after ischemia (three-fold), while kinin B2 receptor mRNA upregulation peaked 24 to 48 h after MCAO (10- to 12-fold versus naïve brain tissue). Immunohistochemistry revealed that kinin B2 receptors were constitutively and widely expressed in mouse brain, were upregulated 2 h after ischemia in cells showing signs of ischemic damage, and remained upregulated in the penumbra up to 24 h after ischemia. B2-/- mice had improved motor function (P<0.05), smaller infarct volumes (-38%; P<0.01), developed less brain edema (-87%; P<0.05), and survived longer (P<0.01) as compared with wild-type controls. The current results show that bradykinin is produced in the brain, kinin B2 receptors are upregulated on dying cells, and B2 receptors are involved in cell death and brain edema formation after experimental stroke.

Photoluminescence Enhancement of Silole-Capped Silicon Quantum Dots Based on Förster Resonance Energy Transfer.

Photoluminescent porous silicon were prepared by an electrochemical etch of n-type silicon under the illumination with a 300 W tungsten filament bulb for the duration of etch. The red photoluminescence emitting at 650 nm with an excitation wavelength of 450 nm is due to the quantum confinement of silicon quantum dots in porous silicon. HO-terminated red luminescent PS was obtained by an electrochemical treatment of fresh PS with the current of 150 mA for 60 seconds in water and sodium chloride. As-prepared PS was sonicated, fractured, and centrifuged in toluene solution to obtain photoluminescence silicon quantum dots. Dichlorotetraphenylsilole exhibiting an emission band at 520 nm was reacted with HO-terminated silicon quantum dots to give a silole-capped silicon quantum dots. The optical characterization of silole-derivatized silicon quantum dots was investigated by UV-vis and fluorescence spectrometer. The fluorescence emission efficiency of silole-capped silicon quantum dots was increased by about 2.5 times due to F6rster resonance energy transfer from silole moiety to silicon quantum dots.

Leukocyte-endothelium interactions during permanent focal cerebral ischemia in mice.

The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 +/- 13.2/100 microm x min and 22.5 +/- 7.9/100 microm x min, respectively at 120 minutes after MCAO (P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 +/- 3.0/100 microm x min rolling and 3.0 +/- 3.6/100 microm x min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.

Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice.

Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood-brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

Detection of nerve agent stimulants based on photoluminescent porous silicon interferometer.

Porous silicon (PSi) exhibiting dual optical properties, both Fabry-Pérot fringe and photolumincence, was developed and used as chemical sensors. PSi samples were prepared by an electrochemical etch of p-type silicon under the illumination of 300-W tungsten lamp during the etch process. The surface of PSi was characterized by cold field-emission scanning electron microscope. PSi samples exhibited a strong visible orange photoluminescence at 610 nm with an excitation wavelength of 460 nm as well as Fabry-Pérot fringe with a tungsten light source. Both reflectivity and photoluminescence were simultaneously measured under the exposure of organophosphate vapors. An increase of optical thickness and quenching photoluminescences under the exposure of various organophosphate vapors were observed.

Contribution of bradykinin receptors to the development of secondary brain damage after experimental subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is the stroke subtype with the highest mortality and morbidity. Which molecular events mediate brain damage after SAH is not well understood. OBJECTIVE: To investigate the role of proinflammatory bradykinin B(1) and B(2) receptors for the pathophysiology of SAH. METHODS: B(1) and B(2) receptor knockout or wild-type mice were subjected to SAH by endovascular puncture. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure were continuously monitored up to 60 minutes after SAH. Brain water content was quantified 24 hours after SAH; mortality, neurological function, and body weight were assessed daily for 7 days after hemorrhage. RESULTS: Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure did not differ between groups. Mortality was 60% in wild-type mice and 82% in B(1)R mice but only 20% in B(2)R animals (P < .05). B(2)R mice also exhibited less severe neurological deficits (P < .05), a less pronounced loss of body weight (P < .05), and significantly less brain edema formation (P < .05) compared with wild-type mice. CONCLUSION: Signaling mediated by bradykinin B(2) receptors contributes to mortality and secondary brain damage after SAH in mice. Thus, B(2) receptors may represent novel targets for the treatment of SAH.

Temporal profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice.

Traumatic brain injury (TBI) is associated with an almost immediate reduction in cerebral blood flow (CBF). Because cerebral perfusion pressure is often normal under these circumstances it was hypothesized that the reduction of post-traumatic CBF has to occur at the level of the microcirculation. The aim of the current study was to investigate whether cerebral microvessels are involved in the development of blood flow disturbances following experimental TBI. C57/BL6 mice (n = 12) were intubated and ventilated under control of end-tidal Pco(2) ((ET)P(CO2)). After preparation of a cranial window and baseline recordings, the animals were subjected to experimental TBI by controlled cortical impact (CCI; 6 m/sec, 0.5 mm). Vessel lumina and intravascular cells were visualized by in vivo fluorescence microscopy (IVM) using the fluorescent dyes FITC-dextran and rhodamine 6G, respectively. Vessel diameter, cell-endothelial interactions, and thrombus formation were quantified within the traumatic penumbra by IVM up to 2 h after CCI. Arteriolar diameters increased after CCI by 26.2 +/- 2.5% (mean +/- SEM, p < 0.01 versus baseline), and remained at this level until the end of the observation period. Rolling of leukocytes on the cerebrovascular endothelium was observed both in arterioles and venules, while leukocyte-platelet aggregates were found only in venules. Microthrombi occluded up to 70% of venules and 33% of arterioles. The current data suggest that the immediate post-traumatic decrease in peri-contusional blood flow is not caused by arteriolar vasoconstriction, but by platelet activation and the subsequent formation of thrombi in the cerebral microcirculation.

Distraction vs remodeling surgery for craniosynostosis.

OBJECTS: We designed several distraction devices and applied these instruments in 14 patients with varying types of craniosynostosis. The aim of this report is to clarify the advantages and disadvantages of these surgical methods and to discuss current concepts for the surgical strategy in the treatment of craniosynostosis. METHODS: From January 2000 to July 2005, 28 patients with craniosynostosis were retrospectively analyzed. Surgical treatment was performed on 14 patients using the distraction method with internal distraction devices that we designed, in which 5 patients had plagiocephaly, 3 brachycephaly, and 6 scaphocephaly. All patients underwent preoperative and postoperative evaluations, which included the patient's neurological state, and three-dimensional CT. RESULTS: With distraction devices, the time required for the surgery could be shortened almost 3 1/3 h; the bleeding during the surgery was decreased with reduced requirement of more than 200 ml of blood transfusion as compared with remodeling surgery. Postoperatively achieved distraction distances varied from 30.0 to 47.5 mm (mean, 42.99 mm). The average increased volume percent of cranium in distraction surgery group was 20.9% (range, -11.5 to 58.9%) after full distraction. CONCLUSION: With distraction surgery, satisfactory cranial volume expansion and aesthetically pleasing morphological states were achieved in all cases, and the efficacy was statistically significantly high as compared with remodeling method.