In-plane anisotropy of graphene by strong interlayer interactions with van der Waals epitaxially grown MoO3.

van der Waals (vdW) epitaxy can be used to grow epilayers with different symmetries on graphene, thereby imparting unprecedented properties in graphene owing to formation of anisotropic superlattices and strong interlayer interactions. Here, we report in-plane anisotropy in graphene by vdW epitaxially grown molybdenum trioxide layers with an elongated superlattice. The grown molybdenum trioxide layers led to high p-doping of the underlying graphene up to p = 1.94 × 1013 cm-2 regardless of the thickness of molybdenum trioxide, maintaining a high carrier mobility of 8155 cm2 V-1 s-1. Molybdenum trioxide-induced compressive strain in graphene increased up to -0.6% with increasing molybdenum trioxide thickness. The asymmetrical band distortion of molybdenum trioxide-deposited graphene at the Fermi level led to in-plane electrical anisotropy with a high conductance ratio of 1.43 owing to the strong interlayer interaction of molybdenum trioxide-graphene. Our study presents a symmetry engineering method to induce anisotropy in symmetric two-dimensional (2D) materials via the formation of asymmetric superlattices with epitaxially grown 2D layers.

The crystal structure of Capicua HMG-box domain complexed with the ETV5-DNA and its implications for Capicua-mediated cancers.

Capicua (CIC) is a transcriptional repressor and functions downstream of the receptor tyrosine kinase (RTK) signaling pathway. Somatic mutations found in the HMG-box DNA binding domain in CIC have been implicated in several cancers such as oligodendroglioma, oligoastrocytoma, and adenocarcinoma. However, the molecular basis of the DNA binding of CIC and the effect of the somatic mutations found in cancers on DNA binding have not been investigated. Here, we report the crystal structure of the HMG-box domain of CIC complexed with its target DNA, the promoter of Ets Translocation Variant 5 (ETV5). The structure shows that the HMG-box domain has an L-shaped structure and recognizes the minor groove leading to DNA bending. Our structure combined with an electrophoretic mobility shift assay (EMSA) revealed that cancer-associated mutations in the HMG-box domain abrogate the interaction with DNA. These results provide the molecular insight into the DNA binding of CIC and reveal the effects of carcinogenic mutations on DNA binding.

Novel DNA Aptamers that Bind to Mutant Huntingtin and Modify Its Activity.

The CAG repeat expansion that elongates the polyglutamine tract in huntingtin is the root genetic cause of Huntington's disease (HD), a debilitating neurodegenerative disorder. This seemingly slight change to the primary amino acid sequence alters the physical structure of the mutant protein and alters its activity. We have identified a set of G-quadruplex-forming DNA aptamers (MS1, MS2, MS3, MS4) that bind mutant huntingtin proximal to lysines K2932/K2934 in the C-terminal CTD-II domain. Aptamer binding to mutant huntingtin abrogated the enhanced polycomb repressive complex 2 (PRC2) stimulatory activity conferred by the expanded polyglutamine tract. In HD, but not normal, neuronal progenitor cells (NPCs), MS3 aptamer co-localized with endogenous mutant huntingtin and was associated with significantly decreased PRC2 activity. Furthermore, MS3 transfection protected HD NPCs against starvation-dependent stress with increased ATP. Therefore, DNA aptamers can preferentially target mutant huntingtin and modulate a gain of function endowed by the elongated polyglutamine segment. These mutant huntingtin binding aptamers provide novel molecular tools for delineating the effects of the HD mutation and encourage mutant huntingtin structure-based approaches to therapeutic development.

Huntingtin's spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function.

The polyglutamine expansion in huntingtin protein causes Huntington's disease. Here, we investigated structural and biochemical properties of huntingtin and the effect of the polyglutamine expansion using various biophysical experiments including circular dichroism, single-particle electron microscopy and cross-linking mass spectrometry. Huntingtin is likely composed of five distinct domains and adopts a spherical α-helical solenoid where the amino-terminal and carboxyl-terminal regions fold to contain a circumscribed central cavity. Interestingly, we showed that the polyglutamine expansion increases α-helical properties of huntingtin and affects the intramolecular interactions among the domains. Our work delineates the structural characteristics of full-length huntingtin, which are affected by the polyglutamine expansion, and provides an elegant solution to the apparent conundrum of how the extreme amino-terminal polyglutamine tract confers a novel property on huntingtin, causing the disease.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats.

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 µg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 µg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 µg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 µg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 µg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Comparison of radiological and clinical results of balloon kyphoplasty according to anterior height loss in the osteoporotic vertebral fracture.

BACKGROUND CONTEXT: Percutaneous kyphoplasty is effective for pain reduction and vertebral height restoration in patients with osteoporotic vertebral fractures. However, in cases of severely collapsed fractures involving the loss of more than 70% of the vertebral height, kyphoplasty is technically difficult to perform and the outcomes remain unknown. PURPOSE: To compare the vertebral height restoration rate, kyphotic angle, and clinical results of patients who underwent kyphoplasty according to the degree of anterior vertebral height loss. In addition, to determine the feasibility and effects of kyphoplasty on severely collapsed osteoporotic vertebral fractures. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: A total of 129 patients (145 vertebrae) who underwent kyphoplasty for osteoporotic painful vertebral fracture and followed up for more than 1 year between September 2005 and August 2012 were recruited for the analysis. OUTCOME MEASURES: The patients' kyphotic angle, anterior vertebral height, and anterior vertebral height restoration ratio 1 year after surgery were compared. Pre- and postoperative pain around the fractured vertebra and the radiological and clinical results according to bone mineral density (BMD) were also compared. METHODS: Patients were divided into three groups for comparison, according to radiographic findings. Patients with an anterior height compression ratio more than 70% at the time of fracture comprised Group I, patients with a compression ratio of 50-70% comprised Group II, and those with a compression ratio of 30-50% comprised Group III. RESULTS: Group I showed a greater extent of anterior height restoration immediately after surgery compared with the other groups, which noticeably decreased over time. All three groups showed significant restoration of the anterior vertebral height between pre- and postoperative values. The anterior vertebral height 1 year after surgery did not differ between Group I and Group II but was significantly higher in Group III. There was no correlation between the BMD and restoration or decrease of anterior vertebral height over time. Pain around the fractured vertebra significantly decreased in all groups immediately and 1 year after surgery compared with preoperative levels, although the pain level 1 year after surgery did not differ significantly between the groups. CONCLUSIONS: In patients with an anterior vertebral compression ratio more than 70% because of osteoporotic vertebral fracture, although the anterior height and kyphotic angle were significantly lower than those of patients with an anterior vertebral compression ratio of 30% to 50%, kyphoplasty significantly improved the degree of pain, restored the anterior vertebral height, and maintained the kyphotic angle. Therefore, kyphoplasty can be a useful approach in patients with an anterior vertebral compression ratio more than 70%.

A comparison of dynamic views using plain radiographs and thin-section three-dimensional computed tomography in the evaluation of fusion after posterior lumbar interbody fusion surgery.

BACKGROUND CONTEXT: Accurate evaluation of the postsurgery status of interbody fusion is important in deciding the patient's treatment. Dynamic plain radiographs are used as a convenient method, but the accuracy is not so good. PURPOSE: This study aimed to evaluate the usefulness of dynamic flexion-extension radiographs as a method for evaluating fusion, by comparing it with three-dimensional thin-section computed tomography (CT). STUDY DESIGN: Prospective controlled study. METHODS: We conducted a prospective study with 108 patients (158 levels) who, diagnosed with severe spinal stenosis and Grade I and Grade II spondylolisthesis, underwent posterior lumbar interbody fusion (PLIF) surgery, with follow-up by dynamic plain radiographs, functional rating scale, and three-dimensional (3D) thin-section CT for 1 year after surgery. In the plain radiographs, we looked for less than 3° of lordotic angle change, less than 3 mm of translation between vertebral bodies, and no presence of halo signs; satisfying all the criteria was regarded as fusion (Group A), whereas failure to satisfy any condition was referred to as probable nonfusion (Group B) and if none were satisfied as nonfusion (Group C). The patients were classified into fusion or nonfusion groups based on CT. Correlation between plain radiographs and CT groups was analyzed. Moreover, clinical assessment and cross-comparison between observers were done. RESULTS: In 158 levels, 95 (60.8%) levels were classified into the fusion group by plain radiographs and 131 (83%) levels by CT. When we analyzed the results of each groups, in Group A, 78 (81.3%) levels belonged to the CT fusion group and 18 (18.7%) levels to the CT nonfusion group, in Group B, 51 (89.5%) and 6 (10.5%) levels, and in Group C, 2 (40%) and 3 (60%) levels, respectively. For each of the CT fusion group, a cross-comparison using dynamic radiographs reconfirmed 78 (59.5%) levels for Group A, 51 (38.9%) levels for Group B, and 2 (1.6%) levels for Group C; for the CT nonfusion groups, 18 (66.7%) levels, 6 (22.2%) levels, and 3 (11.1%) levels were for Groups A, B, and C, respectively. In clinical evaluation, all groups showed clear postsurgery improvement, but there was no statistically significant difference. In terms of observer-to-observer error and agreement between diagnoses, CT showed a statistically higher level of correlation than plain radiographs. CONCLUSIONS: Dynamic flexion-extension radiographs cannot be seen as an objective standard in the evaluation of fusion after PLIF surgery. It would be desirable to confirm the fusion status by thin-section 3D-CT for an objective analysis.

The efficacy of carotid tubercle as an anatomical landmark for identification of cervical spinal level in the anterior cervical surgery: comparison with preoperative C-arm fluoroscopy.

BACKGROUND: In cervical anterior approach, transverse skin incision is preferred due to cosmetic reasons. Precise skin incision is required to reach the surgery segment while minimizing soft tissue injury. Skin incision site is frequently identified using C-arm fluoroscopy or the carotid tubercle. Accordingly, this study was conducted to investigate the efficacy of skin incision using the carotid tubercle as a marker. METHODS: This study was retrospectively conducted on 114 patients who underwent anterior cervical surgery by the same surgeon from April 2004 to June 2012. The rate of the appropriate insertion of K-wire, which was inserted into the disc after anterior approach, into the surgery segment was compared between 62 patients where skin incision site was identified using C-arm fluoroscopy before skin incision and 52 patients where skin incision site was identified using carotid tubercle palpitation before surgery. RESULTS: The needle was shown to have been inserted into the planned site in 106 patients out of the total 114 patients. The appropriate insertion of the needle was shown in 59 patients of group I (95.2%) and in 47 patients of group II (90.4%). Although the success rate was higher in group I than group II, it was statistically insignificant. The success rate of one-segment surgery was shown to be 89.7% in group I and 82.6% in group II. Although the success rate was higher in group I than group II, it was statistically insignificant. The success rate of two-segment surgery was shown to be 100% in group I, and 96.4% in group II due to one case of the failure at C3-4 and C5-6. The success rate of three- and four-segment surgeries was shown to be 100% in both groups. CONCLUSIONS: The identification of skin incision site via carotid tubercle palpation was useful for surgeries involving two or more segments. Furthermore, it could be useful for one-segment surgery if surgical site is identified using vertebral body or soft tissues such as longus collis rather than insertion into the disc.

Long distance fiber Bragg grating strain sensor interrogation using a high speed Raman-based Fourier domain mode-locked fiber laser with recycled residual Raman pump.

We propose a novel fiber Bragg grating (FBG) sensor interrogation using a Raman-based Fourier-domain mode locking (FDML) fiber laser for a high speed and long distance measurement. A residual Raman pump after the generation of the Raman-based FDML fiber laser is recycled for secondary signal amplification in a 2-m erbium-doped fiber (EDF) to further enhance the output power. The chromatic dispersion is precisely controlled to suppress the phase noise in the FDML laser cavity, resulting in the improvement of an R-number of 1.43 mm/dB. After recycling residual pump, we achieve the 40-km round trip transmission of the sensing probe signal with a high scan rate of 30.8 kHz. With 205-mW residual pump power, the bandwidth and the maximum gain are measured to be more than 50 nm, 10.3 dB at 1550 nm, respectively. The sensitivity of the proposed Raman-based FDML fiber laser to strain is also measured, which are 0.81 pm/µstrain in the spectral domain and 0.19 ns/µstrain in the time domain, respectively.

Normal range of the inflammation related laboratory findings and predictors of the postoperative infection in spinal posterior fusion surgery.

BACKGROUND: Inflammation related hematological parameters vary greatly depending on patients. It is not well known how much increase of which parameter warrants suspicion of postoperative infection. This study proposes to identify the normal range and the predictive factors for postoperative infection by conducting a time series analysis of the hematological parameters of patients after the spinal posterior fusion. METHODS: A retrospective study was done with 608 patients who underwent spinal posterior fusion with pedicle screw fixation. Laboratory assessment including the leucocyte, neutrophil, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) of patients for 2 weeks after operation. The patients were divided into the one-level fusion group (group I), the two-level fusion group (group II), the three or multi-level fusion or reoperation group (group III), and the postoperative infection group (group IV). Blood was drawn before breakfast prior to the operation, and then 2-3 days, 4-7 days, 8-11 days, and 12-14 days after the operation. The leucocyte count, neutrophil count, CRP, and ESR were measured. RESULTS: From 4-7 days after the operation, the CRP and neutrophil count of group IV were significantly higher than those of group I and II, and from 8-11 days after operation, the CRP and neutrophil counts were significantly higher than those of all groups. Twelve to fourteen days after the operation, the neutrophil count of group IV was significantly higher than that of group I and II, while the neutrophil count of group III was also higher than that of group I. The lower limit of the 95% confidence interval (CI) of the CRP and neutrophil count group IV was greater than the upper limit of the 95% CI of group I and II. The ESR of group IV was significantly higher than that of group I and III. CONCLUSIONS: If the postoperative CRP and neutrophil counts are high, or if the CRP begins to rise again 8 days after the operation, the likelihood of infection increases, but caution must be exercised in interpreting the results. If the hematological parameters are higher than the lower limit of the 95% CI of the postoperative infection group, infection must be strongly suspected.

Effect of cigarette filters on the chemical composition and in vitro biological activity of cigarette mainstream smoke.

The objective of this study was to evaluate the effects of cigarette filters on the chemical composition and toxicity of cigarette mainstream smoke. In this work, we used three types of cigarettes, including non-filter 2R4F cigarettes, cellulose acetate (CA)-filter 2R4F cigarettes, and carbon dual-filter 2R4F cigarettes. The cytotoxicity of TPM obtained from the filter cigarettes was not different from that of the non-filter cigarettes on an equal TPM basis. However, the EC50 value of GVP from carbon-filter cigarettes were 40.9 puffs/L, thereby indicating the cytotoxicity of these cigarettes was approximately 37% and 21% lower than non-filter and CA-filter cigarettes, respectively. The cytotoxicity of GVP was correlated with carbonyl components. The mutagenicity of TPM obtained from non-filter cigarettes, calculated on an equal TPM basis, was up to 30-40% lower than that of the filter cigarettes. When calculated on a per cigarette basis, the mutagenicity of CA or carbon-filter cigarettes was found to be 35% lower than that of the non-filter cigarettes. The results of chemical composition analyses revealed that the observed increase in aromatic amine compound yields on an equal TPM basis in filter cigarettes may be related with the mutagenic activity determined in Ames assays.