Ultraconfined Plasmonic Hotspots Inside Graphene Nanobubbles.

We report on a nanoinfrared (IR) imaging study of ultraconfined plasmonic hotspots inside graphene nanobubbles formed in graphene/hexagonal boron nitride (hBN) heterostructures. The volume of these plasmonic hotspots is more than one-million-times smaller than what could be achieved by free-space IR photons, and their real-space distributions are controlled by the sizes and shapes of the nanobubbles. Theoretical analysis indicates that the observed plasmonic hotspots are formed due to a significant increase of the local plasmon wavelength in the nanobubble regions. Such an increase is attributed to the high sensitivity of graphene plasmons to its dielectric environment. Our work presents a novel scheme for plasmonic hotspot formation and sheds light on future applications of graphene nanobubbles for plasmon-enhanced IR spectroscopy.

Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival.

BACKGROUND: Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits ≤ 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS: Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS: Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS: This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.

Optimizing broadband terahertz modulation with hybrid graphene/metasurface structures.

We demonstrate efficient terahertz (THz) modulation by coupling graphene strongly with a broadband THz metasurface device. This THz metasurface, made of periodic gold slit arrays, shows near unity broadband transmission, which arises from coherent radiation of the enhanced local-field in the slits. Utilizing graphene as an active load with tunable conductivity, we can significantly modify the local-field enhancement and strongly modulate the THz wave transmission. This hybrid device also provides a new platform for future nonlinear THz spectroscopy study of graphene.

Controlling graphene ultrafast hot carrier response from metal-like to semiconductor-like by electrostatic gating.

We investigate the ultrafast terahertz response of electrostatically gated graphene upon optical excitation. We observe that the photoinduced terahertz absorption increases in charge neutral graphene but decreases in highly doped graphene. We show that this transition from semiconductor-like to metal-like response is unique for zero bandgap materials such as graphene. In charge neutral graphene photoexcited hot carriers effectively increase electron and hole densities and increase the conductivity. In highly doped graphene, however, photoexcitation does not change net conducting carrier concentration. Instead, it mainly increases electron scattering rate and reduce the conductivity.

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.

BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

Imaging and dynamics of light atoms and molecules on graphene.

Observing the individual building blocks of matter is one of the primary goals of microscopy. The invention of the scanning tunnelling microscope revolutionized experimental surface science in that atomic-scale features on a solid-state surface could finally be readily imaged. However, scanning tunnelling microscopy has limited applicability due to restrictions in, for example, sample conductivity, cleanliness, and data acquisition rate. An older microscopy technique, that of transmission electron microscopy (TEM), has benefited tremendously in recent years from subtle instrumentation advances, and individual heavy (high-atomic-number) atoms can now be detected by TEM even when embedded within a semiconductor material. But detecting an individual low-atomic-number atom, for example carbon or even hydrogen, is still extremely challenging, if not impossible, via conventional TEM owing to the very low contrast of light elements. Here we demonstrate a means to observe, by conventional TEM, even the smallest atoms and molecules: on a clean single-layer graphene membrane, adsorbates such as atomic hydrogen and carbon can be seen as if they were suspended in free space. We directly image such individual adatoms, along with carbon chains and vacancies, and investigate their dynamics in real time. These techniques open a way to reveal dynamics of more complex chemical reactions or identify the atomic-scale structure of unknown adsorbates. In addition, the study of atomic-scale defects in graphene may provide insights for nanoelectronic applications of this interesting material.

Charge-carrier screening in single-layer graphene.

The effect of charge-carrier screening on the transport properties of a neutral graphene sheet is studied by directly probing its electronic structure. We find that the Fermi velocity, Dirac point velocity, and overall distortion of the Dirac cone are renormalized due to the screening of the electron-electron interaction in an unusual way. We also observe an increase of the electron mean free path due to the screening of charged impurities. These observations help us to understand the basis for the transport properties of graphene, as well as the fundamental physics of these interesting electron-electron interactions at the Dirac point crossing.

Surface atom motion to move iron nanocrystals through constrictions in carbon nanotubes under the action of an electric current.

Under the application of electrical currents, metal nanocrystals inside carbon nanotubes can be bodily transported. We examine experimentally and theoretically how an iron nanocrystal can pass through a constriction in the carbon nanotube with a smaller cross-sectional area than the nanocrystal itself. Remarkably, through in situ transmission electron imaging and diffraction, we find that, while passing through a constriction, the nanocrystal remains largely solid and crystalline and the carbon nanotube is unaffected. We account for this behavior by a pattern of iron atom motion and rearrangement on the surface of the nanocrystal. The nanocrystal motion can be described with a model whose parameters are nearly independent of the nanocrystal length, area, temperature, and electromigration force magnitude. We predict that metal nanocrystals can move through complex geometries and constrictions, with implications for both nanomechanics and tunable synthesis of metal nanoparticles.

Ripping graphene: preferred directions.

The understanding of crack formation due to applied stress is key to predicting the ultimate mechanical behavior of many solids. Here we present experimental and theoretical studies on cracks or tears in suspended monolayer graphene membranes. Using transmission electron microscopy, we investigate the crystallographic orientations of tears. Edges from mechanically induced ripping exhibit straight lines and are predominantly aligned in the armchair or zigzag directions of the graphene lattice. Electron-beam induced propagation of tears is also observed. Theoretical simulations account for the observed preferred tear directions, attributing the observed effect to an unusual nonmonotonic dependence of graphene edge energy on edge orientation with respect to the lattice. Furthermore, we study the behavior of tears in the vicinity of graphene grain boundaries, where tears surprisingly do not follow but cross grain boundaries. Our study provides significant insights into breakdown mechanisms of graphene in the presence of defective structures such as cracks and grain boundaries.

Subangstrom edge relaxations probed by electron microscopy in hexagonal boron nitride.

Theoretical research on the two-dimensional crystal structure of hexagonal boron nitride (h-BN) has suggested that the physical properties of h-BN can be tailored for a wealth of applications by controlling the atomic structure of the membrane edges. Unexplored for h-BN, however, is the possibility that small additional edge-atom distortions could have electronic structure implications critically important to nanoengineering efforts. Here we demonstrate, using a combination of analytical scanning transmission electron microscopy and density functional theory, that covalent interlayer bonds form spontaneously at the edges of a h-BN bilayer, resulting in subangstrom distortions of the edge atomic structure. Orbital maps calculated in 3D around the closed edge reveal that the out-of-plane bonds retain a strong π(*) character. We show that this closed edge reconstruction, strikingly different from the equivalent case for graphene, helps the material recover its bulklike insulating behavior and thus largely negates the predicted metallic character of open edges.

Raman spectroscopy study of rotated double-layer graphene: misorientation-angle dependence of electronic structure.

We present a systematic Raman study of unconventionally stacked double-layer graphene, and find that the spectrum strongly depends on the relative rotation angle between layers. Rotation-dependent trends in the position, width and intensity of graphene 2D and G peaks are experimentally established and accounted for theoretically. Our theoretical analysis reveals that changes in electronic band structure due to the interlayer interaction, such as rotational-angle dependent Van Hove singularities, are responsible for the observed spectral features. Our combined experimental and theoretical study provides a deeper understanding of the electronic band structure of rotated double-layer graphene, and leads to a practical way to identify and analyze rotation angles of misoriented double-layer graphene.

Probing the out-of-plane distortion of single point defects in atomically thin hexagonal boron nitride at the picometer scale.

Crystalline systems often lower their energy by atom displacements from regular high-symmetry lattice sites. We demonstrate that such symmetry lowering distortions can be visualized by ultrahigh resolution transmission electron microscopy even at single point defects. Experimental investigation of structural distortions at the monovacancy defects in suspended bilayers of hexagonal boron nitride (h-BN) accompanied by first-principles calculations reveals a characteristic charge-induced pm symmetry configuration of boron vacancies. This symmetry breaking is caused by interlayer bond reconstruction across the bilayer h-BN at the negatively charged boron vacancy defects and results in local membrane bending at the defect site. This study confirms that boron vacancies are dominantly present in the h-BN membrane.

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

Tunable superconducting phase transition in metal-decorated graphene sheets.

We have produced graphene sheets decorated with a nonpercolating network of nanoscale tin clusters. These metal clusters both efficiently dope the graphene substrate and induce long-range superconducting correlations. We find that despite structural inhomogeneity on mesoscopic length scales (10-100 nm), this material behaves electronically as a homogenous dirty superconductor with a field-effect tuned Berezinskii-Kosterlitz-Thouless transition. Our facile self-assembly method establishes graphene as an ideal tunable substrate for studying induced two-dimensional electronic systems at fixed disorder and our technique can readily be extended to other order parameters such as magnetism.

Carbon nanotubes as nanoscale mass conveyors.

The development of manipulation tools that are not too 'fat' or too 'sticky' for atomic scale assembly is an important challenge facing nanotechnology. Impressive nanofabrication capabilities have been demonstrated with scanning probe manipulation of atoms and molecules on clean surfaces. However, as fabrication tools, both scanning tunnelling and atomic force microscopes suffer from a loading deficiency: although they can manipulate atoms already present, they cannot efficiently deliver atoms to the work area. Carbon nanotubes, with their hollow cores and large aspect ratios, have been suggested as possible conduits for nanoscale amounts of material. Already much effort has been devoted to the filling of nanotubes and the application of such techniques. Furthermore, carbon nanotubes have been used as probes in scanning probe microscopy. If the atomic placement and manipulation capability already demonstrated by scanning probe microscopy could be combined with a nanotube delivery system, a formidable nanoassembly tool would result. Here we report the achievement of controllable, reversible atomic scale mass transport along carbon nanotubes, using indium metal as the prototype transport species. This transport process has similarities to conventional electromigration, a phenomenon of critical importance to the semiconductor industry.

Rotational actuators based on carbon nanotubes.

Nanostructures are of great interest not only for their basic scientific richness, but also because they have the potential to revolutionize critical technologies. The miniaturization of electronic devices over the past century has profoundly affected human communication, computation, manufacturing and transportation systems. True molecular-scale electronic devices are now emerging that set the stage for future integrated nanoelectronics. Recently, there have been dramatic parallel advances in the miniaturization of mechanical and electromechanical devices. Commercial microelectromechanical systems now reach the submillimetre to micrometre size scale, and there is intense interest in the creation of next-generation synthetic nanometre-scale electromechanical systems. We report on the construction and successful operation of a fully synthetic nanoscale electromechanical actuator incorporating a rotatable metal plate, with a multi-walled carbon nanotube serving as the key motion-enabling element.

Communications: Nanomagnetic shielding: High-resolution NMR in carbon allotropes.

The understanding and control of the magnetic properties of carbon-based materials is of fundamental relevance in applications in nano- and biosciences. Ring currents do play a basic role in those systems. In particular the inner cavities of nanotubes offer an ideal environment to investigate the magnetism of synthetic materials at the nanoscale. Here, by means of (13)C high resolution NMR of encapsulated molecules in peapod hybrid materials, we report the largest diamagnetic shifts (down to -68.3 ppm) ever observed in carbon allotropes, which is connected to the enhancement of the aromaticity of the nanotube envelope upon doping. This diamagnetic shift can be externally controlled by in situ modifications such as doping or electrostatic charging. Moreover, defects such as C-vacancies, pentagons, and chemical functionalization of the outer nanotube quench this diamagnetic effect and restore NMR signatures to slightly paramagnetic shifts compared to nonencapsulated molecules. The magnetic interactions reported here are robust phenomena independent of temperature and proportional to the applied magnetic field. The magnitude, tunability, and stability of the magnetic effects make the peapod nanomaterials potentially valuable for nanomagnetic shielding in nanoelectronics and nanobiomedical engineering.

Tuning nanoelectromechanical resonators with mass migration.

We demonstrate tuning of nanoelectromechanical resonators via mass migration. Indium nanoparticles can be reversibly migrated to different locations along cantilevered multiwalled carbon nanotube resonators using electrical currents as the control parameter. Nonvolatile mass redistributions result in stable resonant frequency shifts as large as 20%. The tuning method is robust and can be utilized for nanoelectromechanical resonators operating at frequencies from audio to microwave.

Nanoscale reversible mass transport for archival memory.

We report on a simple electromechanical memory device in which an iron nanoparticle shuttle is controllably positioned within a hollow nanotube channel. The shuttle can be moved reversibly via an electrical write signal and can be positioned with nanoscale precision. The position of the shuttle can be read out directly via a blind resistance read measurement, allowing application as a nonvolatile memory element with potentially hundreds of memory states per device. The shuttle memory has application for archival storage, with information density as high as 10(12) bits/in(2), and thermodynamic stability in excess of one billion years.