Investigation of the damping wiggler effect and application on the PAL fourth-generation storage ring.

An investigation of the damping wiggler effect to reduce the emittance in the Pohang Accelerator Laboratory (PAL), a fourth-generation storage ring (4GSR) that uses a multi-bend achromat, is presented. A 4GSR lattice which has reduced emittance and increased dynamic aperture to amplify the synergy with two existing light sources (PLS-II and PAL-XFEL) at PAL is described.

Demonstration of a ring-FEL as an EUV lithography tool.

This paper presents the required structure and function of a ring-FEL as a radiation source for extreme ultraviolet radiation lithography (EUVL). A 100 m-long straight section that conducts an extremely low emittance beam from a fourth-generation storage ring can increase the average power at 13.5 nm wavelength to up to 1 kW without degrading the beam in the rest of the ring. Here, simulation results for a ring-FEL as a EUVL source are described.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Femtosecond charge and molecular dynamics of I-containing organic molecules induced by intense X-ray free-electron laser pulses.

We studied the electronic and nuclear dynamics of I-containing organic molecules induced by intense hard X-ray pulses at the XFEL facility SACLA in Japan. The interaction with the intense XFEL pulse causes absorption of multiple X-ray photons by the iodine atom, which results in the creation of many electronic vacancies (positive charges) via the sequential electronic relaxation in the iodine, followed by intramolecular charge redistribution. In a previous study we investigated the subsequent fragmentation by Coulomb explosion of the simplest I-substituted hydrocarbon, iodomethane (CH3I). We carried out three-dimensional momentum correlation measurements of the atomic ions created via Coulomb explosion of the molecule and found that a classical Coulomb explosion model including charge evolution (CCE-CE model), which accounts for the concerted dynamics of nuclear motion and charge creation/charge redistribution, reproduces well the observed momentum correlation maps of fragment ions emitted after XFEL irradiation. Then we extended the study to 5-iodouracil (C4H3IN2O2, 5-IU), which is a more complex molecule of biological relevance, and confirmed that, in both CH3I and 5-IU, the charge build-up takes about 10 fs, while the charge is redistributed among atoms within only a few fs. We also adopted a self-consistent charge density-functional based tight-binding (SCC-DFTB) method to treat the fragmentations of highly charged 5-IU ions created by XFEL pulses. Our SCC-DFTB modeling reproduces well the experimental and CCE-CE results. We have also investigated the influence of the nuclear dynamics on the charge redistribution (charge transfer) using nonadiabatic quantum-mechanical molecular dynamics (NAQMD) simulation. The time scale of the charge transfer from the iodine atomic site to the uracil ring induced by nuclear motion turned out to be only ∼5 fs, indicating that, besides the molecular Auger decay in which molecular orbitals delocalized over the iodine site and the uracil ring are involved, the nuclear dynamics also play a role for ultrafast charge redistribution. The present study illustrates that the CCE-CE model as well as the SCC-DFTB method can be used for reconstructing the positions of atoms in motion, in combination with the momentum correlation measurement of the atomic ions created via XFEL-induced Coulomb explosion of molecules.

Right-to-left shunts as a cause of juxtacortical spots in patients with migraine.

BACKGROUNDS: Juxtacortical spots on fluid-attenuated inversion recovery (FLAIR) images can be frequently detected in patients with migraine. However, the origins of the cerebral lesions (including juxtacortical spots on FLAIR images) found in the previous studies are not known. We sought to investigate the association between juxtacortical spots on FLAIR images and right-to-left shunt (RLS) in migraine patients. METHODS: Juxtacortical spots on FLAIR images were arbitrarily defined as small areas of hyperintensities in the juxtacortex and cortico-subcortical junction. The presence of RLS was examined by a transcranial Dopper (TCD) with the agitated saline test. The degree of RLS was categorized into four grades according to the number of microemboli: no shunt, <10 microbubbles (MB), >10 MB single spots pattern, and >10 MB shower/curtain pattern. We compared the results for migraine patients (n = 49) with those for healthy controls (n = 49). RESULTS: Juxtacortical spots on FLAIR images occurred in 38/98 subjects; of them, 27/49 (55.1%) had migraines and 11/49 (22.2%) were healthy controls (P = 0.002). The independent factors associated with juxtacortical spots on FLAIR images were female, migraine patients, and RLS by multivariate analysis. In migraine patients, RLS was independently associated with juxtacortical spots on FLAIR images. CONCLUSION: Our results suggest that juxtacortical spots on FLAIR images were frequently found in migraine patients and might be associated with the presence of RLS in those patients. Further studies are needed to assess whether juxtacortical spots have clinical implications in patients with migraine.

Biotribological investigation of a multi-tube foot for traction generation in a medical microrobot.

In recent years, efforts to develop microrobots for medical applications have been expanding. One of the key design issues in such microrobots is to attain adequate frictional interaction between the robotic foot and the organ tissue. In particular, it is important to generate the necessary frictional force without damaging the tissue. In this work, a design for the robotic foot was proposed on the basis of the frictional behaviour of a tube structure. Fundamental experiments were initially performed to understand the biotribological behaviour of the tube and rod structures. The design was then modified to a multi-tube structure to achieve adequate frictional behaviour. Biotribological investigation of a multi-tube foot in contact with a small intestine specimen of a pig was conducted using a pin-on-reciprocator type biotribotester. It was found that there is an optimum number and arrangement of the tubes for generating high frictional force. Experimental results showed that a nine-tube foot had the highest initial friction coefficient of about 1.5. The major frictional mechanism was determined to be interlocking between the tubes and the surface structures of the intestine specimen. The results of this work will aid the optimum design of frictional surface for medical microrobots and other biological devices.

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium.

The incidence and clinical aspects of seizures remain to be elucidated in patients with acute pesticide intoxication. The present study included subjects who ingested pesticide with the intention of committing suicide and were treated at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and December 2014. We analyzed the incidence and characterized the type and frequency of seizure, from the medical records of 464 patients with acute pesticide intoxication, according to the pesticide class. The effect of seizure on the clinical outcome was assessed. The incidence of seizure was 31.5% in patients who ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl] butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after seizure initiation, following treatment with antiseizure medication. Generalized tonic-clonic seizures were the most commonly observed (85.7% of the cases). Multivariable logistic regression analysis showed that the effect of seizure on mortality was not statistically significant. In conclusion, glufosinate ammonium herbicide is the most common seizurogenic pesticide class. Seizure itself was not a risk factor for mortality in patients with acute glufosinate ammonium intoxication.

Analytical model development for the prediction of the frictional resistance of a capsule endoscope inside an intestine.

For the purpose of optimizing the design of the locomotion mechanism as well as the body shape of a self-propelled capsule endoscope, an analytical model for the prediction of frictional resistance of the capsule moving inside the small intestine was first developed. The model was developed by considering the contact geometry and viscoelasticity of the intestine, based on the experimental investigations on the material properties of the intestine and the friction of the capsule inside the small intestine. In order to verify the model and to investigate the distributions of various stress components applied to the capsule, finite element (FE) analyses were carried out. The comparison of the frictional resistance between the predicted and the experimental values suggested that the proposed model could predict the frictional force of the capsule with reasonable accuracy. Also, the FE analysis results of various stress components revealed the stress relaxation of the intestine and explained that such stress relaxation characteristics of the intestine resulted in lower frictional force as the speed of the capsule decreased. These results suggested that the frontal shape of the capsule was critical to the design of the capsule with desired frictional performance. It was shown that the proposed model can provide quantitative estimation of the frictional resistance of the capsule under various moving conditions inside the intestine. The model is expected to be useful in the design optimization of the capsule locomotion inside the intestine.

Single-site mutations induce 3D domain swapping in the B1 domain of protein L from Peptostreptococcus magnus.

BACKGROUND: Thermodynamic and kinetic studies of the Protein L B1 domain (Ppl) suggest a folding pathway in which, during the folding transition, the first beta hairpin is formed while the second beta hairpin and the alpha helix are largely unstructured. The same mutations in the two beta turns have opposite effects on the folding and unfolding rates. Three of the four residues composing the second beta turn in Ppl have consecutive positive phi angles, indicating strain in the second beta turn. RESULTS: We have determined the crystal structures of the beta turn mutants G55A, K54G, and G15A, as well as a core mutant, V49A, in order to investigate how backbone strain affects the overall structure of Ppl. Perturbation of the hydrophobic interactions at the closed interface by the V49A mutation triggered the domain swapping of the C-terminal beta strand that relieved the strain in the second beta turn. Interestingly, the asymmetric unit of V49A contains two monomers and one domain-swapped dimer. The G55A mutation escalated the strain in the second beta turn, and this increased strain shifted the equilibrium toward the domain-swapped dimer. The K54G structure revealed that the increased stability is due to the reduction of strain in the second beta turn, while the G15A structure showed that increased strain alone is insufficient to trigger domain swapping. CONCLUSIONS: Domain swapping in Ppl is determined by the balance of two opposing components of the free energy. One is the strain in the second beta turn that favors the dimer, and the other is the entropic cost of dimer formation that favors the monomer. A single-site mutation can disrupt this balance and trigger domain swapping.

A breakdown of symmetry in the folding transition state of protein L.

The 62 residue IgG binding domain of protein L consists of a central alpha-helix packed on a four-stranded beta-sheet formed by N and C-terminal beta-hairpins. The overall topology of the protein is quite symmetric: the beta-hairpins have similar lengths and make very similar interactions with the central helix. Characterization of the effects of 70 point mutations distributed throughout the protein on the kinetics of folding and unfolding reveals that this symmetry is completely broken during folding; the first beta-hairpin is largely structured while the second beta-hairpin and helix are largely disrupted in the folding transition state ensemble. The results are not consistent with a "hydrophobic core first" picture of protein folding; the first beta-hairpin appears to be at least as ordered at the rate limiting step in folding as the hydrophobic core.

The single helix in protein L is largely disrupted at the rate-limiting step in folding.

To investigate the role of helix formation in the folding of protein L, a 62 residue alpha/beta protein, we studied the consequences of both single and multiple mutations in the helix on the kinetics of folding. A triple mutant with 11 additional carbon atoms in core residues in the amino-terminal portion of the helix folded substantially faster than wild type, suggesting that hydrophobic association with residues elsewhere in the protein occurs at the rate-limiting step in folding. However, helix-destabilizing mutations had little effect on the rate of folding; in particular, a triple glycine substitution on the solvent-exposed side of the helix increased the unfolding rate 56-fold while reducing the folding rate less than threefold. Thus, in contrast to the predictions of models of folding involving the coalescence of well-formed secondary structure elements, the single helix in protein L appears to be largely disrupted at the rate-limiting step in folding and unfolding.

Robustness of protein folding kinetics to surface hydrophobic substitutions.

We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.

Scrub typhus encephalomyelitis with prominent focal neurologic signs.

BACKGROUND: Encephalomyelitis with prominent focal neurologic signs and associated neuroradiologic abnormalities has not been previously described in scrub typhus. CASE DESCRIPTION: A 22-year-old woman was admitted because of fever and an altered mental state. Neurologic examination revealed bilateral sixth and seventh nerve palsies, bilateral gaze evoked nystagmus, anarthria, dysphagia, quadriparesis, and sensory level at T1. Serum and cerebrospinal fluid samples were positive for tsutsugamushi antibody. The patient's magnetic resonance images demonstrated the lesions responsible for the neurologic dysfunctions: in the lower brainstem, cerebellar peduncles, and spinal cord. It was interesting that the gray matter of the spinal cord was predominantly involved. CONCLUSIONS: The recognition of unusual manifestations and the clinical suspicion of this treatment-responsive disease may be important, particularly in the face of increasing international and intranational travel.

Sensory dermatomal representation in the medial lemniscus.

BACKGROUND: Restricted sensory deficits along the somatotopic topography of the medial lemniscus rarely develop in medial medullary infarction. We describe a patient with medial medullary infarction who presented with dermatomal sensory deficits caused by a medial lemniscal lesion. CASE DESCRIPTION: A 58-year-old man presented with sudden right-sided hemiparesis and paresthesia. He had noticed the paresthesia below the level of the right L5 dermatome, where his vibration and position senses were mildly diminished. His paresthesia was more severe over the right calf and foot. Magnetic resonance images of the brain showed an acute small infarct in the medial-ventral portion of the left rostral medulla oblongata. A nerve conduction study and electromyography showed no abnormalities. At follow-up, the patient's motor and sensory deficits had improved considerably. CONCLUSIONS: The patient showed lemniscal sensory deficits below the right L5 dermatome that were caused by the partial involvement of the medial lemniscus. These findings suggest that lemniscal sensory dermatomal representation is preserved at least up to the level of the medulla oblongata.

Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study.

OBJECTIVE: To describe an unusual case of hypoglycemia-induced bilateral cerebellar dysfunction. BACKGROUND: The cerebellum is known to be resistant to hypoglycemia, and selective cerebellar dysfunction caused by hypoglycemia has not been reported. Previous studies showed that the ratio between the rate constants for glucose uptake and phosphorylation (K1 and k3) is reversed in the cerebellum compared with the cerebral cortex; higher K1 in the cerebellum and higher k3 in the cerebral cortex. METHODS: Quantitative dynamic PET scanning with labeled fluorodeoxyglucose (18F-FDG) was performed to prove altered glucose kinetics in the cerebellum of a patient who presented with episodic cerebellar dysfunction associated with hypoglycemia. Four control subjects underwent the same study. RESULTS: The ratio between K1 and k3 was not reversed in the cerebellum of our patient (K1 = 0.082, k3 = 0.192). On the contrary, the ratio was reversed in the control subjects (mean K1 = 0.109, mean k3 = 0.080). In addition, the patient's cerebellar metabolic rate of glucose (rCMRglu = 27.9 micromol/100 g/minute) and the rate constant of glucose egress (k2 = 0.543) were relatively increased compared with those of control subjects (mean rCMRglu = 21.9 micromol/100 g/minute, mean k2 = 0.352). CONCLUSIONS: In a case of episodic bilateral cerebellar dysfunction caused by hypoglycemia, quantitative dynamic PET study demonstrated decreased glucose uptake-to-utilization ratio and increased leak of glucose in the cerebellum. The cerebellum is not invariably resistant to hypoglycemia.

The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts.

The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor necrosis factor-alpha), was studied in a human osteoblast cell line (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB transcription factor. When added to MG-63 cells, tumor necrosis factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which has been reported to be a potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-alpha stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha-induced NF-kappaB activation and both NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the TNF-alpha-stimulated osteoblasts. In addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.

A 50 EW/cm;2 Ti:sapphire laser system for studying relativistic light-matter interactions.

A 10-Hz repetition rate, 60-TW peak power, Ti:sapphire laser system was developed for use in experiments where relativistic effects dominate the physics. The temporal, spectral, energy and spatial characteristics of the laser pulses were measured in single shot format. The pulse duration ranged from 22 fs to 25 fs and the pulse energy averaged 1.3 J. Atomic photoionization measurements quantified the peak intensity of the laser pulse in situ. The measurements indicated an intensity of at least 510 19 W/cm 2 was produced.

Cerebral venous thrombosis associated with tentorial subdural hematoma during oxymetholone therapy.

Androgen was reported to cause cerebral venous thrombosis (CVT) during replacement therapy for aplastic anemia. Oxymetholone, a synthetic androgen analogue, has been widely used in the treatment of aplastic anemia. A 40-year-old woman with aplastic anemia visited our hospital because of severe headache, nausea, vomiting, blurred vision and diplopia for a period of 1 month. She had taken oxymetholone for 2 years. Neurological examination revealed bilateral papilledema and bilateral sixth nerve palsies. Brain magnetic resonance imaging (MRI), performed at the time of admission, demonstrated left-sided tentorial SDH, and focal cerebral thrombosis of the left superficial sylvian vein and sigmoid sinus. MR venography revealed multiple irregularities in the superior sagittal sinus and left transverse sinus. CVT with tentorial subdural hematoma (SDH) caused by oxymetholone was strongly suggested. Oxymetholone was immediately discontinued, and her symptoms and signs disappeared. Because of the thrombocytopenia, anticoagulation was not started. She was discharged and visited the outpatient clinic without neurological symptoms for 6 months. This report supports the cautions given about the risk of CVT with oxymetholone supplementation in aplastic anemia. To the best of our knowledge, this is the first report of CVT associated with tentorial SDH that was probably caused by oxymetholone.

The 2003 Carl A Moyer Award: real-time metabolic monitors, ischemia-reperfusion, titration endpoints, and ultraprecise burn resuscitation.

Real-time metabolic monitoring of varied vascular beds provides the raw data necessary to conduct ultraprecise burn shock resuscitation based on second-by-second assessment of regional tissue perfusion. It also illustrates shortcomings of current clinical practices. Arterial base deficit was continuously monitored during 11 clinical resuscitations of patients suffering burn shock using a Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8 ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported laser Doppler images of actual burn wound capillary perfusion. With current clinical therapy, continuous monitoring of arterial base deficit revealed repetitive cycles of resolution/worsening/resolution during burn shock resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic circulation differed depending on the rate of fluid resuscitation (P <.01 between sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound pCO2 values correlated well with laser Doppler determination of actual capillary perfusion (rho = -.48, P <.01). The following conclusions were reached: 1). Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current clinical therapy as demonstrated by numerous "false starts" in the resolution of arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid administration; and 3). burn wound and splanchnic pCO2 are highly correlated with direct measurement of burn wound capillary perfusion by laser Doppler imager. Either technique can serve as a resuscitation endpoint for real-time feedback-controlled ultraprecise resuscitation.