A "Two-Step" Electrochemical Approach for Recovery of Plutonium and Uranium from Aqueous Acidic Waste Solutions.

Chemical quality control of nuclear fuel, particularly the determination of Pu and U contents by chemical methods, results in analytical acidic aqueous waste solutions from which Pu and U must be recovered efficiently for the remediation of radioactive wastes. Reported methods involve several complicated steps requiring addition of chemical oxidants/reductants for valence adjustments and generation of secondary wastes, thereby making the recovery process cumbersome. Herein, we report a novel two-step electrochemical approach for Pu and U recovery from acidic aqueous waste solutions containing different metallic impurities (Fe, Cr, Mn, Cd, Al, Ni, Co, Zn, and Mg) by bulk electrolysis using a Pt gauze electrode. Pu and U are recovered from these waste solutions in a two-step process: (i) bulk electrolysis of the mixed solution at a constant potential of 0.1 V vs Ag/AgCl/3 M KCl that results in the reduction of PuO22+ to Pu3+ followed by the precipitation of Pu3+ as K2(K0.5Pu0.5)(SO4)2, which is then filtered and separated and (ii) the filtrate solution is again subjected to bulk electrolysis at a constant potential of -0.35 V vs Ag/AgCl/3 M KCl resulting in the reduction of UO22+ to U4+. The U4+ is then precipitated as K2(K0.67U0.33)(SO4)2, which is filtered and separated, leading to a Pu- and U-free aqueous acidic waste solutions. Biamperometry shows that 97.8% and 99.1% recovery of Pu and U, respectively, is possible, and emission spectrometry confirms the purity of K2(K0.5Pu0.5)(SO4)2 and K2(K0.67U0.33)(SO4)2. Because of its operational simplicity, potential for remote handling, and excellent extraction efficiency, the present methodology can easily replace traditional methods for the recovery of Pu and U from acidic aqueous waste solutions.

Nitric acid concentration strongly influences low level uranium determination on PEDOT-PSS coated glassy carbon electrodes.

Understanding the parametric optimization and addition of modifications in existing techniques are the keys to successful research in the analytical sciences. The present study reports an electroanalytical technique by modifying an electrode with PEDOT-PSS and adjusting the analyte solution to lower acidity (0.05 M) levels. The proposed methodology achieved a detection limit of 1.24 ppb of uranium, which is far below the available concentrations of uranium in seawater; the WHO permissible limit for uranium in drinking water; and the allowed disposal limit for uranium in radioactive waste solutions. Redox characteristics and speciation analysis supported by theoretical prediction helped to understand the basic mechanism which lay behind the achievement of such low detection limits. The technique was successfully employed for uranium determination in real water samples and the results were validated by another independent technique (ICP-MS).

Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging.

OBJECTIVES: To date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease. METHODS: In this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG4-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68Ga-FAP inhibitor (FAPI)-04), 18F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, 18F-FDG and 68Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data. RESULTS: Using combination of 68Ga-FAPI-04 and 18F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG4+ cells in histology, while 68Ga-FAPI-04 PET positive lesions showed abundant activated fibroblasts expressing FAP according to results from RNA-sequencing of activated fibroblasts. The responsiveness of fibrotic lesions to anti-inflammatory treatment was far less pronounced than that of inflammatory lesions. CONCLUSION: FAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG4-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG4-related disease, as subtypes dominated by fibrosis may require different approaches to control disease progression, for example, specific antifibrotic agents rather than broad spectrum anti-inflammatory treatments such as glucocorticoids.

Economic impact of contact force sensing in catheter ablation for atrial fibrillation.

AIMS: The TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) clinical trial compared clinical outcomes using a contact force (CF) sensing ablation catheter (TactiCath) with a catheter that lacked CF measurement. This analysis links recorded events in the TOCCASTAR study and a large claims database, IBM MarketScan®, to determine the economic impact of using CF sensing during atrial fibrillation (AF) ablation. METHODS AND RESULTS: Clinical events including repeat ablation, use of antiarrhythmic drugs, hospitalization, perforation, pericarditis, pneumothorax, pulmonary edema, pulmonary vein stenosis, tamponade, and vascular access complications were adjudicated in the year after ablation. CF was characterized as optimal if greater than or equal to 90% lesion was performed with greater than or equal to 10 g of CF. A probabilistic 1:1 linkage was created for subjects in MarketScan® with the same events in the year after ablation, and the cost was evaluated over 10 000 iterations. Of the 279 subjects in TOCCASTAR, 145 were ablated using CF (57% with optimal CF), and 134 were ablated without CF. In the MarketScan® cohort, 9811 subjects who underwent AF ablation were used to determine events and costs. For subjects ablated with optimal CF, total cost was $19 271 ± 3705 in the year after ablation. For ablation lacking CF measurement, cost was $22 673 ± 3079 (difference of $3402, P < .001). In 73% of simulations, optimal CF was associated with lower cost in the year after ablation. CONCLUSION: Compared to ablation without CF, there was a decrease in healthcare cost of $3402 per subject in the first year after the procedure when optimal CF was used.

Interplay of Coriolis effect with rheology results in unique blood dynamics on a compact disc.

We investigate the influence of rotational forces on blood dynamics in a microfluidic device. The special confluence of Coriolis force and blood rheology is brought forth by analyzing the flow at different hematocrit (volume fraction of red blood cells) levels and rotational speeds. We further study the effects of channel layout and alignment with regard to the axis of rotation to understand this intricate interplay. We provide a sound basis for efficient designing of a lab on a compact disc (lab on CD) platform by harnessing the effects of Coriolis force at relatively much lower rotational speeds, in sharp contrast with the reported findings where Coriolis effects have been considered to be effective only for exceptionally high rotational speeds. Our results show that over certain intermediate regimes of rotational speeds, the flow profiles for different hematocrit levels are noticeably different. This, in turn, could be harnessed as a possible diagnostic signature of the hematocrit (or equivalently, packed cell volume) level, without necessitating the deployment of chemical consumables, in an energy efficient paradigm.

Anion Exchange in II-VI Semiconducting Nanostructures via Atomic Templating.

Controlled chemical transformation of nanostructures is a promising technique to obtain precisely designed novel materials, which are difficult to synthesize otherwise. We report high-temperature vapor-phase anion-exchange reactions to chemically transform II-VI semiconductor nanostructures (100-300 nm length scale) while retaining the single crystallinity, crystal structure, morphology, and even defect distribution of the parent material via atomic templating. The concept of atomic templating is employed to obtain kinetically controlled, thermodynamically metastable structural phases such as zincblende CdSe and CdS from zincblende CdTe upon complete chemical replacement of Te with Se or S. The underlying transformation mechanisms are explained through first-principles density functional theory calculations. Atomic templating is a unique path to independently tune materials' phase and composition at the nanoscale, allowing the synthesis of novel materials.

Description of new "epsilon sign" and its significance in reduction in highly unstable variant of intertrochanteric fracture.

BACKGROUND: Intertrochanteric fractures are commonly encountered in day-to-day trauma practice having various fracture patterns. Adequate reduction and appropriate fixation methodology is required for optimum results. However, failure rates are very high in unstable fractures. Here we describe a unique unstable variant of intertrochanteric fracture characterized by a long spike of proximal fragment, irreducibility of fracture with standard traction and internal rotation and soft tissue interposition. This appears as typical figure of 3 signs on right side and epsilon ε sign on left side on AP X-ray of pelvis with both hips. MATERIALS AND METHODS: In retrospective review of 924 intertrochanteric fractures treated at our institution from June 2005 to January 2017, twenty patients with this typical highly unstable fracture pattern (epsilon sign/figure of 3 at fracture site) were operated at our institution, which included 18 males and two females with average age of 43.5 years (range 30-60 years). All patients required open reduction with specific maneuver and dynamic hip screw fixation. RESULTS: All patients had good reduction at the end of surgery, and all patients had good signs of clinico-radiological union at follow-up. None of the patients had implant loosening or screw back out. CONCLUSION: The typical radiological pattern seen on X-ray will guide the surgeon to predict this unstable variant of IT fracture preoperatively and will suggest toward requirement of open reduction with specific maneuver and internal fixation with dynamic hip screw.

Impact of Practice-Based Management of Pulmonary Artery Pressures in 2000 Patients Implanted With the CardioMEMS Sensor.

BACKGROUND: Elevated pulmonary artery (PA) pressures in patients with heart failure are associated with a high risk for hospitalization and mortality. Recent clinical trial evidence demonstrated a direct relationship between lowering remotely monitored PA pressures and heart failure hospitalization risk reduction with a novel implantable PA pressure monitoring system (CardioMEMS HF System, St. Jude Medical). This study examines PA pressure changes in the first 2000 US patients implanted in general practice use. METHODS: Deidentified data from the remote monitoring Merlin.net (St. Jude Medical) database were used to examine PA pressure trends from the first consecutive 2000 patients with at least 6 months of follow-up. Changes in PA pressures were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mm Hg-day) during the follow-up period relative to the baseline pressure. As a reference, the PA pressure trends were compared with the historic CHAMPION clinical trial (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association [NYHA] Functional Class III Heart Failure Patients). The area under the curve results are presented as mean±2 SE, and P values comparing the area under the curve of the general-use cohort with outcomes in the CHAMPION trial were computed by the t test with equal variance. RESULTS: Patients were on average 70±12 years old; 60% were male; 34% had preserved ejection fraction; and patients were followed up for an average of 333±125 days. At implantation, the mean PA pressure for the general-use patients was 34.9±10.2 mm Hg compared with 31.3±10.9 mm Hg for CHAMPION treatment and 32.0±10.5 mm Hg for CHAMPION control groups. The general-use patients had an area under the curve of -32.8 mm Hg-day at the 1-month time mark, -156.2 mm Hg-day at the 3-month time mark, and -434.0 mm Hg-day after 6 months of hemodynamic guided care, which was significantly lower than the treatment group in the CHAMPION trial. Patients consistently transmitted pressure information with a median of 1.27 days between transmissions after 6 months. CONCLUSIONS: The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.

Poly(3,4-ethylenedioxythiophene)-Poly(styrenesulfonate)-Coated Glassy-Carbon Electrode for Simultaneous Voltammetric Determination of Uranium and Plutonium in Fast-Breeder-Test-Reactor Fuel.

Uranium (U) and plutonium (Pu) contents in nuclear materials must be maintained to a definite level in order to get the desired performance of the fuel inside the reactor. Therefore, high accuracy and precision is an essential criterion for the determination of U and Pu. We already reported the voltammetric determination of Pu in the presence of U in fast-breeder-test-reactor (FBTR) fuel samples, but interfacial, coupled chemical reactions between U(IV) and Pu(IV) enhance the peak-current density of U(VI) reduction and thus make voltammetry unsuitable for the quantitative determination of U in the presence of Pu. Thus, developing a voltammetric method for the simultaneous determination of U and Pu is highly challenging. Herein, we report the simultaneous voltammetric determination of U and Pu in 1 M sulfuric acid (H2SO4) on a poly(3,4-ethylenedioxythiophene) (PEDOT)-poly(styrenesulfonate) (PSS)-modified glassy-carbon (GC) electrode (PEDOT-PSS/GC). The modified electrode shows enhanced performance compared with bare GC electrodes. The peak-current density for U(VI) reduction is enhanced in the presence of Pu(IV), but it attains saturation when [Pu]/[U] in solution is maintained ≥2. Hence, under these circumstances, the variation of Pu concentration no longer influences the U(VI)-reduction peak, and thus the quantitative determination of U in the presence of Pu is possible. No interference is observed from commonly encountered impurities present in FBTR fuel samples. This method shows accuracy and precision comparable to those of the biamperometry method. High robustness, fast analysis, simultaneous determination, reduced radiation exposure to the analyst, and ease of recovery of U and Pu from analytical waste makes it a suitable candidate to substitute the presently applied biamperometry method.

Selective Electrochemical Separation and Recovery of Uranium from Mixture of Uranium(VI) and Lanthanide(III) Ions in Aqueous Medium.

Separation of uranium (U) from interfering lanthanide ions (Ln3+) in aqueous medium is important in view of sustainable nuclear power production and remediation of radioactive waste. Separation of U in aqueous medium by electrochemical means is still unexplored. Herein, we report electrochemical separation of U from interfering lanthanides ions in 0.1 M KCl on poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) modified platinum (PEDOT:PSS/Pt) electrode. U in solution commonly exists as uranyl (UO22+). U separation is achieved in a two step process: (i) UO22+ reduction to insoluble urania (UO2) which gets deposited on PEDOT:PSS/Pt in the presence of Ln3+ (La3+, Ce3+, and Sm3+) ions and (ii) oxidation of electrodeposited UO2 to UO22+ in fresh 0.1 M KCl (pH = 2) solution. Electrodeposition of UO2 is confirmed by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Although, the presence of Ln3+ ions in UO22+solution hinders electrodeposition of UO2, but application of more negative reduction potential (-0.6 V vs Ag/AgCl) for longer duration (8 h) results in quantitative electrodeposition of UO2. Inductively coupled plasma mass spectrometry (ICP-MS) shows that 94% (±10%) recovery of UO22+ is possible from mixed solution of UO22+and Ln3+ ions on PEDOT:PSS/Pt electrode.

Design, synthesis and in vitro study of densely functionalized oxindoles as potent α-glucosidase inhibitors.

Diabetes a non-communicable disease occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicated an increase in the trend of people diagnosed with type 2 diabetes mainly due to unhealthy life style. Here in we report a new class of oxindole derivatives 6a-kvia scaffold hopping of known α-glucosidase inhibitors 1-4. When molecular docking was performed against a homology model of α-glucosidase the resulting compound 6d revealed binding interactions comparable to 1-4. The compounds were accessed through a unique condensation-ring opening protocol of pyridofuranone building blocks. Overall the compounds exhibited decent binding to the yeast α-glucosidase, where the most potent compound 6h, inhibited the enzyme with IC50 of 0.6 µM. This was nearly threefold improvement from the original known compounds 1-4, selected to design the newer analogs. The reaction kinetics of 6h indicated competitive inhibition.

Oral squamous cell carcinoma patients can be differentiated from healthy individuals with label-free serum proteomics.

BACKGROUND: No blood biomarkers to detect early oral cavity squamous cell carcinoma (OSCC) without clinical signs exist - diagnosis is solely based on histology of a visible tumour. Most OSCC patients are diagnosed at advanced stage, which leads to significant morbidity and poor survival. Our aim was to find the serum screening or detection biomarkers in OSCC. METHODS: Serum samples from patients with OSCC treated at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital (Finland) were collected. Age- and gender-matched healthy individuals served as controls. Quantitative label-free proteomics in high definition MSE mode(HDMSE) was performed on 13 patients and 12 healthy samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most influential proteins, which classify the patients vs healthy samples. RESULTS: In quantitative proteomic analysis (HDMSE), 388 proteins were quantified in our pilot study. A complete separation between cases and controls was seen in supervised and unsupervised classification techniques such as orthogonal projections on latent structure-discriminant analysis (OPLS-DA) and self-organising maps. Using OPLS-DA S-plot, we identified a set of eight proteins that completely separated OSCC patients from healthy individuals. CONCLUSIONS: Although the tumour stages varied from I to IVa, these potential biomarkers were able to identify all OSCCs demonstrating their sensitivity to detect tumours of all stages. We are the first to suggest a set of serum biomarkers in our pilot study to be evaluated further as a diagnostic panel to detect preclinical OSCC in risk patients.

Calcium-induced conformational changes of Thrombospondin-1 signature domain: implications for vascular disease.

CONTEXT: Thrombospondin1 (TSP1) participates in numerous signaling pathways critical for vascular physiology and disease. The conserved signature domain of thrombospondin 1 (TSP1-Sig1) comprises three epidermal growth factor (EGF), 13 calcium-binding type 3 thrombospondin (T3) repeats, and one lectin-like module arranged in a stalk-wire-globe topology. TSP1 is known to be present in both calcium-replete (Holo-) and calcium-depleted (Apo-) state, each with distinct downstream signaling effects. OBJECTIVE: To prepare a homology model of TSP1-Sig1 and investigate the effect of calcium on its dynamic structure and interactions. METHODS: A homology model of Holo-TSP1-Sig1 was prepared with TSP2 as template in Swissmodel workspace. The Apo-form of the model was obtained by omitting the bound calcium ions from the homology model. Molecular dynamics (MD) simulation studies (100 ns) were performed on the Holo- and Apo- forms of TSP1 using Gromacs4.6.5. RESULTS AND DISCUSSION: After simulation, Holo-TSP1-Sig1 showed significant reorientation at the interface of the EGF1-2 and EGF2-3 modules. The T3 wire is predicted to show the maximum mobility and deviation from the initial model. In Apo-TSP1-Sig1 model, the T3 repeats unfolded and formed coils with predicted increase in flexibility. Apo-TSP1-Sig1model also predicted the exposure of the binding sites for neutrophil elastase, integrin and fibroblast growth factor 2. We present a structural model and hypothesis for the role of TSP1-Sig1 interactions in the development of vascular disorders. CONCLUSION: The simulated model of the fully calcium-loaded and calcium-depleted TSP1-Sig1 may enable the development of its interactions as a novel therapeutic target for the treatment of vascular diseases.

Altered Expression of Sphingosine-1-Phosphate Metabolizing Enzymes in Oral Cancer Correlate With Clinicopathological Attributes.

We have determined the gene expression of sphingosine-1-phosphate (S1P) metabolizing enzymes (SphK1, SphK2, SGPL1, SGPP1, SGPP2, PPAP2A, PPAP2B, and PPAP2C) by quantitative real-time polymerase chain reaction in tumor tissues and adjacent normal tissues of 50 oral squamous cell carcinoma (OSCC) patients. Expression of SphK1 and SGPP1 genes was up-regulated significantly in 70% and 75% OSCC tumors respectively. Importantly, expression of SphK2 and PPAP2B was down-regulated in the tumor tissues of 70% OSCC patients. Expression of SphK2 and PPAP2B negatively correlated with tumor-node-metastasis (TNM) staging and tumor volume respectively. Furthermore, LPP1 is an independent predictor of TNM staging and lymph node ratio.

Fine mapping of a QTL affecting levels of skatole on pig chromosome 7.

BACKGROUND: Previous studies in the Norwegian pig breeds Landrace and Duroc have revealed a QTL for levels of skatole located in the region 74.7-80.5 Mb on SSC7. Skatole is one of the main components causing boar taint, which gives an undesirable smell and taste to the pig meat when heated. Surgical castration of boars is a common practice to reduce the risk of boar taint, however, a selection for boars genetically predisposed for low levels of taint would help eliminating the need for castration and be advantageous for both economic and welfare reasons. In order to identify the causal mutation(s) for the QTL and/or identify genetic markers for selection purposes we performed a fine mapping of the SSC7 skatole QTL region. RESULTS: A dense set of markers on SSC7 was obtained by whole genome re-sequencing of 24 Norwegian Landrace and 23 Duroc boars. Subsets of 126 and 157 SNPs were used for association analyses in Landrace and Duroc, respectively. Significant single markers associated with skatole spanned a large 4.4 Mb region from 75.9-80.3 Mb in Landrace, with the highest test scores found in a region between the genes NOVA1 and TGM1 (p < 0.001). The same QTL was obtained in Duroc and, although less significant, with associated SNPs spanning a 1.2 Mb region from 78.9-80.1 Mb (p < 0.01). The highest test scores in Duroc were found in genes of the granzyme family (GZMB and GZMH-like) and STXBP6. Haplotypes associated with levels of skatole were identified in Landrace but not in Duroc, and a haplotype block was found to explain 2.3% of the phenotypic variation for skatole. The SNPs in this region were not associated with levels of sex steroids. CONCLUSIONS: Fine mapping of a QTL for skatole on SSC7 confirmed associations of this region with skatole levels in pigs. The QTL region was narrowed down to 4.4 Mb in Landrace and haplotypes explaining 2.3% of the phenotypic variance for skatole levels were identified. Results confirmed that sex steroids are not affected by this QTL region, making these markers attractive for selection against boar taint.

Nanotwin Detection and Domain Polarity Determination via Optical Second Harmonic Generation Polarimetry.

We demonstrate that optical second harmonic generation (SHG) can be utilized to determine the exact nature of nanotwins in noncentrosymmetric crystals, which is challenging to resolve via conventional transmission electron or scanned probe microscopies. Using single-crystalline nanotwinned CdTe nanobelts and nanowires as a model system, we show that SHG polarimetry can distinguish between upright (Cd-Te bonds) and inverted (Cd-Cd or Te-Te bonds) twin boundaries in the system. Inverted twin boundaries are generally not reported in nanowires due to the lack of techniques and complexity associated with the study of the nature of such defects. Precise characterization of the nature of defects in nanocrystals is required for deeper understanding of their growth and physical properties to enable their application in future devices.

Observing Oxygen Vacancy Driven Electroforming in Pt-TiO2-Pt Device via Strong Metal Support Interaction.

Oxygen vacancy formation, migration, and subsequent agglomeration into conductive filaments in transition metal oxides under applied electric field is widely believed to be responsible for electroforming in resistive memory devices, although direct evidence of such a pathway is lacking. Here, by utilizing strong metal-support interaction (SMSI) between Pt and TiO2, we observe via transmission electron microscopy the electroforming event in lateral Pt/TiO2/Pt devices where the atomic Pt from the electrode itself acts as a tracer for the propagating oxygen vacancy front. SMSI, which originates from the d-orbital overlap between Pt atom and the reduced cation of the insulating oxide in the vicinity of oxygen vacancies, was optimized by fabricating nanoscale devices causing Pt atom migration tracking the moving oxygen vacancy front from the anode to cathode during electroforming. Experiments performed in different oxidizing and reducing conditions, which tune SMSI in the Pt-TiO2 system, further confirmed the role of oxygen vacancies during electroforming. These observations also demonstrate that the noble metal electrode may not be as inert as previously assumed.

Transforming Growth Factor-ß Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells.

The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis of hepatocellular carcinoma (HCC). The identification of molecular mechanisms involved in the transmigration of malignant hepatocytes through the endothelial barrier is of high relevance for therapeutic intervention and metastasis prevention. In this study, we employed a model of hepatocellular transmigration that mimics vascular invasion using hepatic sinusoidal endothelial cells and malignant hepatocytes evincing a mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-ß. Labelling of respective cell populations with various stable isotopes and subsequent mass spectrometry analyses allowed the "real-time" detection of molecular changes in both transmigrating hepatocytes and endothelial cells. Interestingly, the proteome profiling revealed 36 and 559 regulated proteins in hepatocytes and endothelial cells, respectively, indicating significant changes during active transmigration that mostly depends on cell-cell interaction rather than on TGF-ß alone. Importantly, matching these in vitro findings with HCC patient data revealed a panel of common molecular alterations including peroxiredoxin-3, epoxide hydrolase, transgelin-2 and collectin 12 that are clinically relevant for the patient's survival. We conclude that hepatocellular plasticity induced by TGF-ß is crucially involved in blood vessel invasion of HCC cells.

PMv Neuronal Firing May Be Driven by a Movement Command Trajectory within Multidimensional Gaussian Fields.

The premotor cortex (PM) is known to be a site of visuo-somatosensory integration for the production of movement. We sought to better understand the ventral PM (PMv) by modeling its signal encoding in greater detail. Neuronal firing data was obtained from 110 PMv neurons in two male rhesus macaques executing four reach-grasp-manipulate tasks. We found that in the large majority of neurons (∼90%) the firing patterns across the four tasks could be explained by assuming that a high-dimensional position/configuration trajectory-like signal evolving ∼250 ms before movement was encoded within a multidimensional Gaussian field (MGF). Our findings are consistent with the possibility that PMv neurons process a visually specified reference command for the intended arm/hand position trajectory with respect to a proprioceptively or visually sensed initial configuration. The estimated MGF were (hyper) disc-like, such that each neuron's firing modulated strongly only with commands that evolved along a single direction within position/configuration space. Thus, many neurons appeared to be tuned to slices of this input signal space that as a collection appeared to well cover the space. The MGF encoding models appear to be consistent with the arm-referent, bell-shaped, visual target tuning curves and target selectivity patterns observed in PMV visual-motor neurons. These findings suggest that PMv may implement a lookup table-like mechanism that helps translate intended movement trajectory into time-varying patterns of activation in motor cortex and spinal cord. MGFs provide an improved nonlinear framework for potentially decoding visually specified, intended multijoint arm/hand trajectories well in advance of movement.