The effect of expectation on facilitation of colour/form conjunction tasks by TMS over area V5

In an earlier paper, we reported task-specific impairments and improvements caused by applying TMS over cortical visual area V5 [Proceedings of the Royal Society of London B 265 (1998) 537]. The phenomenon is further investigated in the present study using two of the previous tasks: a motion/form conjunction in which TMS impaired performance and a colour/form conjunction in which performance was enhanced with TMS. In the earlier experiment, subjects were presented with blocks of trials of one task type perhaps allowing some of the observed effects to arise from knowing the type of stimulus to be discriminated. When blocks of trials consisted of randomly mixed moving/form and colour/form conjunction tasks, TMS over V5 still impaired target-present responses for the moving/form conjunction, but the facilitation seen for colour/form conjunction target-present responses disappeared. We suggest that the competitive inhibition postulated between visual movement areas and colour areas in the brain, in our previous paper, are subject to expectation or knowledge of forthcoming stimulus type

Critical Fields and Critical Currents in MgB2

We review recent measurements of upper (Hc2) and lower (Hc1) critical fields in clean single crystals of MgB2, and their anisotropies between the two principal crystallographic directions. Such crystals are far into the "clean limit" of Type II superconductivity, and indeed for fields applied in the c-direction, the Ginzburg-Landau parameter k is only about 3, just large enough for Type II behaviour. Because m0Hc2 is so low, about 3 T for fields in the c-direction, MgB2 has to be modified for it to become useful for high-current applications. It should be possible to increase Hc2 by the introduction of strong electron scattering (but because of the electronic structure and the double gap that results, the scatterers will have to be chosen carefully). In addition, pinning defects on a scale of a few nm will have to be engineered in order to enhance the critical current density at high fields.Comment: BOROMAG Conference Invited paper. To appear in Supercond. Sci. Tec

Design of 12.5 kA current leads for the Large Hadron Collider using high temperature superconductor material

The Large Hadron Collider will be equipped with about 8000 superconducting magnets. Some 2600 current leads will feed the currents ranging from 25 to 12500 A. CERN aims to reduce the consumption of liquid helium, using high temperature superconductors in these leads. A development of leads for 12.5 kA is being conducted in collaboration with Oxford Instruments. The design options for these leads are described. A test rig and prototype lead have been made according to one of the options. Electrical contact tests are in progress on BSCCO-2212 and YBCO-123 samples. In the first run, the prototype carried 13000 A

HIF1α and HIF2α Exert Distinct Nutrient Preferences in Renal Cells

Background: Hypoxia Inducible Factors (HIF1α and HIF2α) are commonly stabilized and play key roles related to cell growth and metabolic programming in clear cell renal cell carcinoma. The relationship of these factors to discretely alter cell metabolic activities has largely been described in cancer cells, or in hypoxic conditions, where other confounding factors undoubtedly compete. These transcription factors and their specific roles in promoting cancer metabolic phenotypes from the earliest stages are poorly understood in pre-malignant cells. Methods: We undertook an analysis of SV40-transformed primary kidney epithelial cells derived from newborn mice genetically engineered to express a stabilized HIF1α or HIF2α transgene. We examined the metabolic profile in relation to each gene. Results: Although the cells proliferated similarly, the metabolic profile of each genotype of cell was markedly different and correlated with altered gene expression of factors influencing components of metabolic signaling. HIF1α promoted high levels of glycolysis as well as increased oxidative phosphorylation in complete media, but oxidative phosphorylation was suppressed when supplied with single carbon source media. HIF2α, in contrast, supported oxidative phosphorylation in complete media or single glucose carbon source, but these cells were not responsive to glutamine nutrient sources. This finding correlates to HIF2α-specific induction of Glul, effectively reducing glutamine utilization by limiting the glutamate pool, and knockdown of Glul allows these cells to perform oxidative phosphorylation in glutamine media. Conclusion: HIF1α and HIF2α support highly divergent patterns of kidney epithelial cell metabolic phenotype. Expression of these factors ultimately alters the nutrient resource utilization and energy generation strategy in the setting of complete or limiting nutrients

Effective Vortex Pinning in MgB2 thin films

We discuss pinning properties of MgB2 thin films grown by pulsed-laser deposition (PLD) and by electron-beam (EB) evaporation. Two mechanisms are identified that contribute most effectively to the pinning of vortices in randomly oriented films. The EB process produces low defected crystallites with small grain size providing enhanced pinning at grain boundaries without degradation of Tc. The PLD process produces films with structural disorder on a scale less that the coherence length that further improves pinning, but also depresses Tc

FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

AbstractThe mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([18F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2weeks; serial computed tomography (CT) scans were obtained at baseline and every 8weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P=0.01; clear cell subtype P=0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P=0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability.In this phase II trial, FDG-PET was explored as a predictive biomarker for response to everolimus (mTOR inhibition) in metastatic renal cell carcinoma. Everolimus therapy decreased SUVs on follow-up FDG-PET scans in these patients. SUV changes were modestly correlated with changes in tumor size and baseline average SUVmax values were correlated with overall survival

LUMINOS-102: Lerapolturev with and without α-PD- 1 in unresectable α-PD- 1 refractory melanoma

Lerapolturev (lera, formerly PVSRIPO) is a novel poliovirus based intratumoral immunotherapy that infects both cancer cells and antigen-presenting cells (APCs) via CD155, the poliovirus receptor. Lera has direct anticancer effects while also generating type I/III interferon-dominated inflammation and anti-tumor T-cell priming and activation via infection of local APCs. LUMINOS-102 (NCT04577807) is a multi-center, open-label, two-arm randomized Phase 2 study investigating the efficacy and safety of lera ± α-PD- 1 in patients with unresectable melanoma who failed prior α-PD- 1 therapy. Cross-over to the α-PD- 1 arm is permitted after progression, PR for ≥6 mo or 6 mo on treatment with SD. The maximum initial lera dose was 6x108 TCID50 /visit every 3 or 4 weeks (Q3/4 W). As of March 2022, the maximum lera dose was increased to 1.6 x 109 TCID50/visit, every week (QW) for 7 weeks (induction), followed by Q3/4 W dosing (maintenance). As of 20-Jun- 2022, 21 participants (10 male, 11 female, median 64 yrs) received lera (n = 14 at initial dose, Q3/4 W; n = 4 at increased dose, Q3/4 W; n = 3 at increased dose, QW) ± αPD-1. Five patients are currently on treatment. With the initial regimen, no objective responses and a CBR of 7% were observed. However, with the higher dose regimen, 1 complete response and a CBR of 71% (5/7) has been observed. Two of 4 participants with stable disease have evidence of response (1 with resolution of uninjected lung metastasis, 1 with decreased PET signal in injected and uninjected lesions receiving combination therapy). The only treatment related AE in \u3e1 pt was fatigue (19%, all grade 1 or 2). No dose-limiting toxicities or treatment-related SAEs were reported. Multiplex-IF analysis of on-treatment tumor biopsies will be presented. Lera ± αPD-1 is well tolerated, with early signs of efficacy at the higher dose level. Enrollment and randomization are ongoing

Recovery of visual fields in brain-lesioned patients by reaction perimetry treatment

<p>Abstract</p> <p>Background</p> <p>The efficacy of treatment in hemianopic patients to restore missing vision is controversial. So far, successful techniques require laborious stimulus presentation or restrict improvements to selected visual field areas. Due to the large number of brain-damaged patients suffering from visual field defects, there is a need for an efficient automated treatment of the total visual field.</p> <p>Methods</p> <p>A customized treatment was developed for the reaction perimeter, permitting a time-saving adaptive-stimulus presentation under conditions of maximum attention. Twenty hemianopic patients, without visual neglect, were treated twice weekly for an average of 8.2 months starting 24.2 months after the insult. Each treatment session averaged 45 min in duration.</p> <p>Results</p> <p>In 17 out of 20 patients a significant and stable increase of the visual field size (average 11.3° ± 8.1) was observed as well as improvement of the detection rate in the defective visual field (average 18.6% ± 13.5). A two-factor cluster analysis demonstrated that binocular treatment was in general more effective in augmenting the visual detection rate than monocular. Four out of five patients with a visual field increase larger than 10° suffered from hemorrhage, whereas all seven patients with an increase of 5° or less suffered from infarction. Most patients reported that visual field restoration correlated with improvement of visual-related activities of daily living.</p> <p>Conclusion</p> <p>Rehabilitation treatment with the Lubeck Reaction Perimeter is a new and efficient method to restore part of the visual field in hemianopia. Since successful transfer of treatment effects to the occluded eye is achieved under monocular treatment conditions, it is hypothesized that the damaged visual cortex itself is the structure in which recovery takes place.</p