Photothermal response in dual-gated bilayer graphene.

The photovoltaic and bolometric photoresponse in gapped bilayer graphene was investigated by optical and transport measurements. A pulse coincidence technique at 1.5 µm was used to measure the response times as a function of temperature. The bolometric and photovoltaic response times were found to be identical implying that the photovoltaic response is also governed by hot electron thermal relaxation. Response times of τ ∼ 100-20 ps were found for temperatures from 3-100 K. Above 10 K, the relaxation time was observed to be τ = 25 ± 5 ps, independent of temperature within noise.

Synthesis and Characterization of Supported Mixed MoW Carbide Catalysts.

For mixed MoW carbide catalysts, the relationship between synthesis conditions, evolution of (mixed) phases, extent of mixing, and catalytic performance of supported Mo/W carbides remains unclear. In this study, we prepared a series of carbon nanofiber-supported mixed Mo/W-carbide catalysts with varying Mo and W compositions using either temperature-programmed reduction (TPR) or carbothermal reduction (CR). Regardless of the synthesis method, all bimetallic catalysts (Mo:W bulk ratios of 1:3, 1:1, and 3:1) were mixed at the nanoscale, although the Mo/W ratio in individual nanoparticles varied from the expected bulk values. Moreover, the crystal structures of the produced phases and nanoparticle sizes differed depending on the synthesis method. When using the TPR method, a cubic carbide (MeC1-x ) phase with 3-4 nm nanoparticles was obtained, while a hexagonal phase (Me2C) with 4-5 nm nanoparticles was found when using the CR method. The TPR-synthesized carbides exhibited higher activity for the hydrodeoxygenation of fatty acids, tentatively attributed to a combination of crystal structure and particle size.

Universal conductance fluctuations in Dirac materials in the presence of long-range disorder.

We study quantum transport in Dirac materials with a single fermionic Dirac cone (strong topological insulators and graphene in the absence of intervalley coupling) in the presence of non-Gaussian long-range disorder. We show, by directly calculating numerically the conductance fluctuations, that in the limit of very large system size and disorder strength, quantum transport becomes universal. However, a systematic deviation away from universality is obtained for realistic system parameters. By comparing our results to existing experimental data on 1/f noise, we suggest that many of the graphene samples studied to date are in a nonuniversal crossover regime of conductance fluctuations.

High-fidelity conformation of graphene to SiO2 topographic features.

High-resolution noncontact atomic force microscopy of SiO2 reveals previously unresolved roughness at the few-nm length scale, and scanning tunneling microscopy of graphene on SiO2 shows graphene to be slightly smoother than the supporting SiO2 substrate. A quantitative energetic analysis explains the observed roughness of graphene on SiO2 as extrinsic, and a natural result of highly conformal adhesion. Graphene conforms to the substrate down to the smallest features with nearly 99% fidelity, indicating conformal adhesion can be highly effective for strain engineering of graphene.

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.

Re-transplantation from the same unrelated donor in three adolescents with severe aplastic anemia after graft rejection.

Hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD) has become the accepted salvage treatment for patients with severe aplastic anemia (SAA) lacking a matched sibling donor and failing immunosuppressive treatment. However, non-engraftment and early rejection remain main reasons for treatment related morbidity and mortality. We report on three adolescents who were grafted from MUD, rejected their graft and were re-grafted 47-51 days after first HSCT from the same donor. For conditioning, fludarabine, cyclophosphamide, ATG and/or OKT3 in combination with total lymphoid irradiation was used. Unmanipulated peripheral blood stem cells at a minimum dose of 8 x 10(6)/kg CD34+cells were infused. Acute toxicity was low. Two patients are alive and well for more than 3 years, one patient developed extended chronic graft-versus-host disease from which he died 34 months after second HSCT. Re-transplantation from MUD in the case of non-engraftment or rejection from the same donor is possible following immunoablation combined with intensive serotherapy in young patients with SAA.

Allogeneic stem cell transplantation for pediatric and adolescent patients with CML: results from the prospective trial CML-paed I.

PURPOSE: Stem cell transplantation (SCT) can definitely cure chronic myeloid leukemia (CML), a rare disease in childhood. We prospectively evaluated the results of early SCT in pediatric CML after standardized pretreatment with hydroxyurea+/-interferon. PATIENTS AND METHODS: Between 1995 and 2004, 200 children (median age: 12.4 years) were enrolled and stratified: given the availability of an HLA-matched related donor (MRD), SCT was scheduled within 6 months and otherwise from an unrelated donor (UD) within 12 months following diagnosis. RESULTS: 176 patients underwent SCT; from MRD within median 4 months and from UD within median 11 months after diagnosis. At SCT, 158 patients were in chronic phase (CP1 or CP2), 9 patients were in accelerated phase and 9 patients were in blast crisis (BC). The conditioning regimen - total body irradiation or busulfan - exerted no different impact on overall survival (OS). Probability of OS at 5 years was 87+/-11% if grafted from a sibling (n=41), 52+/-9% from matched UD (MUD, n=71), and 45+/-16% from mismatched donors (MMD, n=55), respectively. A trend for better OS in CP1 was observed if SCT was performed within 6 months (n=49; 74+/-9%), compared to 7-12 months (n=52; 62+/-15%), and >12 months (n=43; 62+/-17%) after diagnosis, respectively (p=0.157). Probability of relapse at 5 years was 20+/-12%. Transplant-related mortality and graft-versus-host disease mainly contributed to the inferior outcome in UD and HLA-mismatched SCT. CONCLUSION: These data from the first prospective trial on CML restricted to children and adolescents might be considered for decision making when balancing the risks of SCT against the increasing use of imatinib as upfront treatment for CML.

Hypersensitivity for capsaicin in patients with functional dyspepsia.

The pathophysiology of functional dyspepsia is poorly understood, thus diagnostic and therapeutic options for this disease are limited. We assessed the relevance of a simple test for chemical hypersensitivity by applying an oral capsaicin load. After a preliminary dose-finding study, 61 healthy controls and 54 functional dyspepsia patients swallowed a capsule containing 0.75 mg capsaicin. A graded questionnaire evaluated severity of symptoms before and after capsule ingestion; an aggregate symptom score was calculated by adding all symptom scores. Controls developed moderate symptoms (symptom score: 6.0+/-4.1; median: 5.0). The 75% quartile (9.0) was considered the upper limit of normal. Functional dyspepsia patients had significantly higher symptom scores (10.0+/-6.5) than controls. About 54% of functional dyspepsia patients tested positive; clinically this group was not different from the group testing negative besides being on average younger and suffering more from bloating. In additional 13 patients with functional dyspepsia who tested positive (symptom score: 15.8+/-0.9), symptom response to placebo capsules (1.9+/-0.6) was similar to controls. In reliability testing, the Cronbach alpha-value of the capsaicin test was 0.86. The capsaicin test is a simple and non-invasive method to detect a subgroup of functional dyspepsia with chemical hypersensitivity.

Polymerase chain reaction fingerprinting of Erwinia amylovora has a limited phylogenetic value but allows the design of highly specific molecular markers.

Erwinia amylovora, the causal agent of fire blight, is genetically very homogeneous, and current methodologies provide insufficient or contradictory information about the probable dispersal routes of the pathogen. With the final aim to obtain specific and reliable molecular markers for different lineages of the pathogen, we studied the molecular basis of rep-polymerase chain reaction (PCR) polymorphism using seven different arbitrary primers to fingerprint 93 E. amylovora strains from different countries, including Spain. Polymorphism was very low, and was displayed by only 11 E. amylovora strains, which produced 22 polymorphic bands. Five of 11 polymorphic bands cloned contained DNA that was present in more than 85% of the strains, whereas six bands were due to DNA present exclusively in the strains producing the rep-PCR polymorphism. Also, five of the polymorphic bands were due to the possession of either the ubiquitous plasmid pEA29, of plasmid pEU30, which was exclusively found in strains from North America, or of a 35-kb cryptic plasmid, present only in 28 strains from Northern Spain. We designed primer pairs from several cloned polymorphic bands that allowed the specific identification of the strains producing the polymorphism. Our results indicate that rep-PCR is not adequate for constructing genealogies of E. amylovora, although the strategy illustrated here, as well as the designed primers, can be used effectively in epidemiological studies with this pathogen.

Intestinal chemo- and mechano-sensitivity: selective modification of small intestinal sensitivity by lipids.

BACKGROUND: Intestinal chemo-nociception is a recently described mechanism of perception of intraluminal stimuli that might involve pathways independent from mechano-nociception. AIM: To investigate whether intraluminal lipids not only modify mechano-sensitivity, but also influence chemo-sensitivity. METHOD: Nineteen healthy volunteers ingested an orojejunal tube assembly for mechanical and chemical stimulation of the proximal jejunum. Volume-controlled distension of a jejunal balloon and capsaicin perfusion were performed during simultaneous infusion of saline or a 10% lipid emulsion. A standard questionnaire evaluated quality and intensity of symptoms induced by intestinal stimulation. RESULTS: Balloon volumes to induce perception thresholds were significantly reduced during lipid perfusion (P < 0.05), while balloon pressures remained unaltered (P > 0.05). Saline infusion (2.5 mL/min) did not alter thresholds of perception. Lipid infusion also increased intensity of perception during given distension volumes (P < 0.05). Lipid infusion did neither affect perception quality induced by capsaicin, nor perception thresholds, nor intensity of perception during capsaicin perfusion (P > 0.05). The quality of sensations induced by capsaicin perfusion was similar to sensations during distension, except of sensation of warmth, that was almost exclusively reported during capsaicin perfusion. CONCLUSIONS: Intraluminal lipids selectively modify intestinal mechano-perception and do not alter chemo-perception. Intestinal chemo-nociception and mechano-nociception are two mechanisms of intestinal perception that involve distinct sensory pathways.

Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood.

Myelodysplastic syndromes (MDS) are a heterogenous group of acquired hematopoietic stem cell disorders. Refractory cytopenia (RC) is the most common subtype of childhood MDS and hematopoietic stem cell transplantation (HSCT) is the only curative treatment. HSCT following a myeloablative preparative regimen is associated with a low probability of relapse and considerable transplant-related mortality. In the present European Working Groups of MDS pilot study, we investigated whether a reduced intensity conditioning regimen (RIC) is able to offer reduced toxicity without increased rates of graft failure or relapse. Nineteen children with RC were transplanted from an unrelated donor following RIC consisting of fludarabine, thiotepa and anti-thymocyte globulin. Three patients experienced graft failure. Neutrophil and platelet engraftment occurred at a median time of 23 and 30 days, respectively. Cumulative incidence of grade II-IV and grade III and IV acute graft-versus-host disease (GVHD) was 0.48 and 0.13, respectively; three patients developed extensive chronic GVHD. Although infections were the predominant complications, only one patient with extensive chronic GVHD died from infectious complications. Overall and event-free survival at 3 years were 0.84 and 0.74, respectively. In conclusion, our results were comparable to those of patients treated with myeloablative HSCT. Long-term follow-up is needed to demonstrate the expected reduction in long-term sequelae.

Clinical characteristics of functional dyspepsia depending on chemosensitivity to capsaicin.

BACKGROUND: Augmented chemosensitivity to capsaicin has been demonstrated in approximately half of functional dyspepsia (FD) patients. AIM: We determined clinical characteristics of FD patients with and without chemical hypersensitivity at baseline and after capsaicin ingestion for 4 weeks. METHODS: N=49 outpatients with confirmed FD received an oral sensitivity test with 0.75 mg capsaicin at three occasions, before and after ingesting 0.25 mg capsaicin tid for 4 weeks. Symptomatic response to capsaicin allowed stratification to a capsaicin positive (chemosensitive) and a capsaicin negative (not chemosensitive) patient group. Symptom diaries were completed in the week before and during capsaicin ingestion. RESULTS: A total of 53% FD had a positive capsaicin test, Crohnbach alpha was 0.85. Basic clinical characteristics were comparable in capsaicin positive and negative FD, but median daily aggregate upper gastrointestinal symptoms scores were significantly higher in capsaicin positive (median: 9.4; 5.4/11.7) than in capsaicin negative patients (6.6; 4.1/8.1) (P<.05). After capsaicin ingestion, upper gastrointestinal symptoms scores were reduced by -3.3 (-4.9/-1.9; P<.001) in capsaicin positive and -2.6 (-3.8/-0.3; P<.05) in capsaicin negative patients. Lower abdominal symptoms were comparable in capsaicin positive and negative patients at baseline (NS). After capsaicin ingestion lower gastrointestinal symptoms scores were reduced by -1.0 (-1.8/-0.1; P<.05) in capsaicin positive but not significantly altered (-0.6; -1.7/+0.9; NS) in capsaicin negative patients. After long-term capsaicin ingestion, the capsaicin test turned negative in 53% of chemosensitive patients (P<.01). CONCLUSIONS: Differences in upper GI symptoms distinguished capsaicin positive and negative patients. Symptom improvement after long-term capsaicin ingestion was indirect proportional to the capsaicin test result.

A specific deletion in the breakpoint cluster region of the ALL-1 gene is associated with acute lymphoblastic T-cell leukemias.

A variety of chromosomal translocations to the ALL-1 gene are regularly observed in acute leukemias and are thought to play a key role in the leukemogenic process. Chimeric proteins are encoded by the breakpoint regions of the derivative chromosomes have been proposed to be the relevant oncogenic agents. In addition, internal duplications of the ALL-1 gene have been observed in patients with specific acute myeloid leukemias. Thus, it has been hypothesized that oncogenic variants of the ALL-1 protein may be generated by both chimerization and self-fusion, but the critical structural features endowing the altered proteins with their oncogenic potential are still unknown. Here a novel structural alteration of the ALL-1 gene was observed in three patients presenting with acute T-cell leukemia (ALL) without chromosomal translocations or self-fusions of the ALL-1 gene. These unrelated patients carried an internal deletion in one of the two alleles of the ALL-1 gene that eliminated parts of introns 7 and 8, together with exon 8. The deletion was found in 3 of 74 ALL patients, but not in acute myeloid leukemias, follicular lymphomas, or peripheral blood leukocytes from healthy donors. One ALL patient showed the deletion at diagnosis but no longer at remission or at 9 months after remission. These findings support the hypothesis that the ALL-1 protein may be converted to an oncogenic variant, not only by chimerization or self-fusion, but also by deletion of sequences coded by exon 8. They further suggest that these three different types of structural alterations of the ALL-1 protein may each cause a distinct disease phenotype. Alternatively spliced mRNA species omitting exon 8 were observed in 14 of 24 ALL patients without detectable macroscopic alterations of the ALL-1 gene and also in peripheral blood leukocytes from healthy donors.

Practical aspects of diffractive imaging using an atomic-scale coherent electron probe.

Four-dimensional scanning transmission electron microscopy (4D-STEM) is a technique where a full two-dimensional convergent beam electron diffraction (CBED) pattern is acquired at every STEM pixel scanned. Capturing the full diffraction pattern provides a rich dataset that potentially contains more information about the specimen than is contained in conventional imaging modes using conventional integrating detectors. Using 4D datasets in STEM from two specimens, monolayer MoS2 and bulk SrTiO3, we demonstrate multiple STEM imaging modes on a quantitative absolute intensity scale, including phase reconstruction of the transmission function via differential phase contrast imaging. Practical issues about sampling (i.e. number of detector pixels), signal-to-noise enhancement and data reduction of large 4D-STEM datasets are emphasized.

Betulinic acid-induced apoptosis in leukemia cells.

Betulinic acid (BA), a natural component isolated from Birch trees, effectively induces apoptosis in neuroectodermal and epithelial tumor cells and exerts little toxicity in animal trials. Here, we show that BA-induced marked apoptosis in 65% of primary pediatric acute leukemia cells and all leukemia cell lines tested. When compared for in vitro efficiency with conventionally used cytotoxic drugs, BA was more potent than nine out of 10 standard therapeutics and especially efficient in tumor relapse. No crossresistances were found between BA and any cytotoxic drug. Intracellular apoptosis signaling in leukemia tumor cells paralleled the pathway found in neuroectodermal cells involving caspases, but not death receptors. In isolated mitochondria, BA induced release of both cytochrome c and Smac. Taken together, BA potently induces apoptosis in leukemia cells and should be further evaluated as a future drug to treat leukemia.

Creating a Stable Oxide at the Surface of Black Phosphorus.

The stability of the surface of in situ cleaved black phosphorus crystals upon exposure to atmosphere is investigated with synchrotron-based photoelectron spectroscopy. After 2 days atmosphere exposure a stable subnanometer layer of primarily P2O5 forms at the surface. The work function increases by 0.1 eV from 3.9 eV for as-cleaved black phosphorus to 4.0 eV after formation of the 0.4 nm thick oxide, with phosphorus core levels shifting by <0.1 eV. The results indicate minimal charge transfer, suggesting that the oxide layer is suitable for passivation or as an interface layer for further dielectric deposition.

Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia.

Allogeneic stem cell transplantation (allo-SCT) is a well-established treatment modality for children with severe aplastic anemia (SAA). Treatment failures are rare and mostly caused by graft rejection. Increasing mixed chimerism represents a stage at the very beginning of graft rejection, where immunological intervention might be an effective prophylactic approach. To substantiate this, we: (1) monitored peripheral blood cells from children with SAA after allo-SCT and performed pre-emptive immunotherapy in patients with increasing MC. In all, 23/34 courses of 32 children with SAA after allo-SCT showed a complete chimerism (CC) throughout and 10/34 developed different types of mixed chimerism (MC). Altogether, 4/10 with MC spontaneously developed decreasing MC, 2/10 courses persisted with low proportions of autologous cells below 30% (stable-MC), 4/10 developed increasing MC and one patient showed an autologous recovery. All patients with CC, decreasing MC or stable MC remained in continuous complete remission (CCR). In all, 2/4 patients with increasing MC developed graft rejection. Based on these observations, 2/4 new patients with increasing MC received low-dose DLIs prophylactically, and remained in CCR without any GVHD. These results substantiate that low-dose DLI in children with SAA and increasing MC can prevent graft rejection with a calculable risk to induce severe GVHD.

Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center.

In children, pulmonary sequelae contribute to early and late morbidity after bone marrow transplantation (BMT). Between 1975-1999, we performed 152 BMTs in 138 pediatric patients with malignant and nonmalignant diseases. Allogenic bone marrow was used from 99 HLA identical siblings and from 23 other related or unrelated donors. Autologous marrow was used in 30 transplantations. Median age was 8. 6 years (range, 1.1-22.4) at time of BMT. The median survival was 42%, the survival time was 6.5 years (range, 0.8-23.1), and the median follow-up time was 6.8 years (range, 0.8-23.2). Seventeen patients had severe respiratory complications. Early severe respiratory complications leading to death within the first 4 months after BMT were due to pulmonary edema (n = 1), or fungal (n = 3), bacterial (n = 1), or viral (n = 2) pneumonia. Late severe respiratory sequelae were defined as persistent respiratory symptoms for more than 4 months despite treatment, and these occurred in 10 patients, of whom 5 died. Underlying diagnoses covered a wide spectrum, including bronchiolitis obliterans (n = 3), severe restrictive lung disease (n = 2), idiopathic pneumonia syndrome (n = 3), chronic bronchitis (n = 1), and hepatopulmonary syndrome (n = 1). The overall probability for death was 0.58, and for death from severe respiratory complications, 0.16. With improved HLA matching, fewer BMTs after relapsed or primary progressive disease, and improved supportive care, including the usage of CMV negative blood products, after 1990 the probability of death from severe respiratory complications was only 0.04, whereas before 1990 it was 0.23 (P = 0.029; in each time period, n = 69). The disease spectrum has changed from initially more infectious complications to bronchiolitis obliterans and idiopathic pneumonia syndrome. Lung function measurements performed in 85 of 138 patients usually showed a mild restrictive pattern. To identify those children as early as possible who are at risk for severe respiratory complications, a close longitudinal follow-up after BMT by pediatric pulmonologists is necessary.

Cognitive factors and CS-UCS interval effects in the differential conditioning and extinction of skin conductance responses.

Mandel and Bridger (1967) found resistance to extinction of differentially conditioned skin conductance responses by subjects, who, according to a post-conditioning questionnaire, believed pre-extinction instructions that the shock-UCS would no longer be administered. The present study was intended to: (1) determine whether or not an extraordinarily noxious shock-UCS is required to produce such results; (2) eliminate possible retrospective falsification effects associated with the use of a post-conditioning questionnaire by monitoring subjects' UCS expectancies continuously throughout extinction as well as acquisition trials; (3) attempt to confirm that resistance to extinction is stronger with a 0.5 sec CS-UCS interval than with an 8 sec interval; and (4) test several predictions regarding UCS expectancies during the intertrial intervals of acquisition. After receiving 16 instructed acquisition trials, two groups (N = 20 in each) exposed to either a 0.5 sec or 8 sec CS-UCS interval were fully instructed regarding discontinuation of the UCS during the pending 20 extinction trials. Reliable differential conditioning was obtained during the first extinction trial block for subjects who, according to the expectancy monitoring measure as well as a post-conditioning questionnaire, did not expect UCS administration. The extent of resistance to extinction did not differ between the two groups. Consistent with predictions from a cognitive viewpoint, the expectancy monitoring data of the two groups differed significantly during the intertrial intervals of acquisition.

When are additive models valid for evaluating proposed research?

This paper is concerned with a comparison of two broad classes of mathematical models, additive and multiplicative, for selecting the best among a number of competing project proposals addressed to a defined research objective. The analysis is predicated on the view that, though additive models are widely utilized, they are theoretically inferior to multiplicative ones. In an effort to more clearly understand when the use of additive models might be acceptable despite their logical flaws, conditions are investigated under which they yield results that are essentially equivalent to those produced by multiplicative models.