Ultra-low contact resistance in graphene devices at the Dirac point

Contact resistance is one of the main factors limiting performance of short-channel graphene field-effect transistors (GFETs), preventing their use in low-voltage applications. Here we investigated the contact resistance between graphene grown by chemical vapor deposition (CVD) and different metals, and found that etching holes in graphene below the contacts consistently reduced the contact resistance, down to 23 Omega . mu m with Au contacts. This low contact resistance was obtained at the Dirac point of graphene, in contrast to previous studies where the lowest contact resistance was obtained at the highest carrier density in graphene (here 200 Omega . mu m was obtained under such conditions). The 'holey' Au contacts were implemented in GFETs which exhibited an average transconductance of 940 S m(-1) at a drain bias of only 0.8 V and gate length of 500 nm, which out-perform GFETs with conventional Au contacts

How healthy is community-dwelling elderly population? Results from southern Italy

PURPOSE To explore the frequency of polypharmacy, functional and cognitive capacity among the elderly in Southern Italy. METHODS Populationbased retrospective cross-sectional study. Information were retrieved from electronic-geriatric-forms matched by record-linkage to outpatient pharmacy-records. The following domains were collected from geriatric forms: BMI, cognitive capacity (SPMSQ), functional status Barthel-index), mobility, living condition. Polypharmacy status was categorized as non-polypharmacy (0-4), polypharmacy (5-9) and excessive-polypharmacy (>10). Prevalence of all variables were stratified by age and polypharmacy group. RESULTS 88,878 old people received a geriatric assessment in the years 2013-2014. Mean age was 74.8 (±7.3) years, 56.6% females. Proportion of elderly in excessive-polypharmacy increased with age (18.9% in 65-75 age-group; 27.9% in >85). Referring to cognitive capacity, the proportion of lucid patients decreased with age (from 94.3% to 58.1%), while confused patient increased with age (from 4.7% to 30.9%). Proportion of subjects with a decline in cognitive status, functional status and mobility increased in polypharmacy and excessive polypharmacy group. CONCLUSION Polypharmacy is common in people aged 65 years and older with difficulties in activities of daily living and impaired cognition. Furthermore, its prevalence raises with increasing age. Preventive strategies such us optimization of drug regimen should be performed routinely to reduce risk of adverse-health-events

Elevated Expression of Squamous Cell Carcinoma Antigen (SCCA) Is Associated with Human Breast Carcinoma

Squamous cell carcinoma antigen (SCCA) belongs to the serine protease inhibitor (Serpin) family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC) in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360) and normal breast epithelium (n = 124). SCCA expression was scored on a tiered scale (0-3) independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%), Grade II (2.5%), and Grade III (9.4%) breast cancers (p<0.0001). Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005). No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124). SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR) double-negative tumors (p = 0.0009). Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively). This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Cascading wafer-scale integrated graphene complementary inverters under ambient conditions

The fundamental building blocks of digital electronics are logic gates which must be capable of cascading such that more complex logic functions can be realized. Here we demonstrate integrated graphene complementary inverters which operate with the same input and output voltage logic levels, thus allowing cascading. We obtain signal matching under ambient conditions with inverters fabricated from wafer-scale graphene grown by chemical vapor deposition (CVD). Monolayer graphene was incorporated in self-aligned field-effect transistors in which the top gate overlaps with the source and drain contacts. This results in full-channel gating and leads to the highest low-frequency voltage gain reported so far in top-gated CVD graphene devices operating in air ambient, Av ~ −5. Such gain enabled logic inverters with the same voltage swing of 0.56 V at their input and output. Graphene inverters could find their way in realistic applications where high-speed operation is desired but power dissipation is not a concern, similar to emitter-coupled logic

Gigahertz Integrated Graphene Ring Oscillators

Ring oscillators (ROs) are the most important class of circuits used to evaluate the performance limits of any digital technology. However, ROs based on low-dimensional nanomaterials (e.g., 1-D nanotubes, nanowires, 2-D MoS2) have so far exhibited limited performance due to low current drive or large parasitics. Here we demonstrate integrated ROs fabricated from wafer-scale graphene grown by chemical vapor deposition. The highest oscillation frequency was 1.28 GHz, while the largest output voltage swing was 0.57 V. Both values remain limited by parasitic capacitances in the circuit rather than intrinsic properties of the graphene transistor components, suggesting further improvements are possible. The fabricated ROs are the fastest realized in any low-dimensional nanomaterial to date and also the least sensitive to fluctuations in the supply voltage. They represent the first integrated graphene oscillators of any kind and can also be used in a wide range of applications in analog electronics. As a demonstration, we also realized the first stand-alone graphene mixers that do not require external oscillators for frequency conversion. The first gigahertz multitransistor graphene integrated circuits demonstrated here pave the way for application of graphene in high-speed digital and analog circuits in which high operating speed could be traded off against power consumption

Scaling of graphene integrated circuits

The influence of transistor size reduction (scaling) on the speed of realistic multi-stage integrated circuits (ICs) represents the main performance metric of a given transistor technology. Despite extensive interest in graphene electronics, scaling efforts have so far focused on individual transistors rather than multi-stage ICs. Here we study the scaling of graphene ICs based on transistors from 3.3 to 0.5 μm gate lengths and with different channel widths, access lengths, and lead thicknesses. The shortest gate delay of 31 ps per stage was obtained in sub-micron graphene ROs oscillating at 4.3 GHz, which is the highest oscillation frequency obtained in any strictly low-dimensional material to date. We also derived the fundamental Johnson limit, showing that scaled graphene ICs could be used at high frequencies in applications with small voltage swing

On-Chip Magnetic Platform for Single-Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high-throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig-zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1-μm sized beads is demonstrated

SCCA expression correlates to high grade breast cancer in the CDP progression TMA.

<p>The three CDP progression TMA case sets (designated as Case Sets 3, 5, and 7 by CDP) were probed for SCCA expression and scored. The grading information was provided by CDP in 291 accountable samples.</p