Paraxial diffusion-field retrieval

Unresolved spatially-random microstructure, in an illuminated sample, can lead to position-dependent blur when an image of that sample is taken using an incoherent imaging system. For a small propagation distance, between the exit surface of the sample and the entrance surface of a position-sensitive detector, the paraxial approximation implies that the blurring influence of the sample may be modeled using an anomalous-diffusion field. This diffusion field may have a scalar or tensor character, depending on whether the random microstructure has an autocorrelation function that is rotationally isotropic or anisotropic, respectively. Partial differential equations are written down and then solved, in a closed-form manner, for several variants of the inverse problem of diffusion-field retrieval given suitable intensity images. Both uniform-illumination and structured-illumination schemes are considered. Links are made, between the recovered diffusion field and certain statistical properties of the unresolved microstructure. The developed theory -- which may be viewed as a crudely parallel form of small-angle scattering under the Guinier approximation -- is applicable to a range of paraxial radiation and matter fields, such as visible light, x rays, neutrons, and electrons

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

Intracerebral electrical stimulations of the temporal lobe: a stereo-electroencephalography study

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large-sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug-resistant focal epilepsy with at least one electrode implanted in this area. We found that high-frequency stimulations were more likely to evoke electroclinical manifestations (p < .0001) and also provoked ‘false positive’ seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p < .0001). Visual symptoms were not associated with after discharge (p = .0002) and were mainly evoked by stimulation of the hippocampus (p = .009) and of the parahippocampal gyrus (p = .0212). ‘False positive seizures’ can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe

Prevalence of suspected hypertrophic cardiomyopathy or left ventricular hypertrophy based on race and gender in teenagers using screening echocardiography

BACKGROUND:The goal of this study was to evaluate the prevalence of suspected hypertrophic cardiomyopathy (HCM) in a population of teenagers undergoing screening echocardiography for the detection of HCM.METHOD:The Anthony Bates Foundation performs screening echocardiography for the prevention of sudden death. A total of 2,066 students were studied between the ages of 13 to 19 years. Suspected HCM was defined as any wall thickness greater than or equal to] 15 mm. LVH was defined as wall thickness greater than or equal to] 13 mmRESULTS:Prevalence of suspected HCM was 0.7% (14/2066). After adjusting for hypertension (HTN), the total prevalence was 0.5% (8/1457). In a subgroup analysis, 551 teenagers with documented race and LV wall thickness were identified between the ages of 13 - 19 years. African American teenagers 6% (3/50)] had higher prevalence of suspected HCM 0.8% (4/501), OR 7.93, CI 1.72-36.49, p = 0.002]. After multivariate adjustment for age, gender, BMI and HTN (systolic BP >140 and diastolic BP of > 90), African American race remained independently associated with suspected HCM (OR 4.89, CI 1.24-39.62, p = 0.02).CONCLUSION:The prevalence of suspected HCM in young teenagers is approximately 0.2%. This prevalence appears to be higher in African Americans. However, due to small number of African Americans in our population, our result needs to be confirmed in larger trials.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Apoptosis as a Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the rela-tionship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC)

Genetic pre-participation screening in selected athletes: a new tool for the prevention of sudden cardiac death?

Sudden cardiac death (SCD) of athletes is a topical issue. “Borderline cardiac abnormalities”, which occur in ~2% of elite male athletes, may result in SCD, which may have a genetic base. Genetic analysis may help identify pathological cardiac abnormalities. We performed phenotype-guided genetic analysis in athletes who, pre-participation, showed ECG and/or echo “borderline” abnormalities, to discriminate subjects at a greater risk of SCD. Methods: We studied 24 elite athletes referred by the National Federation of Olympic sports; and 25 subjects seeking eligibility to practice agonistic sport referred by the Osservatorio Epidemiologico della Medicina dello Sport della Regione Campania. Inclusion criteria: a) ECG repolarization borderline abnormalities; b) benign ventricular arrhythmias; c) left ventricular wall thickness in the grey zone of physiology versus pathology (max wall thickness 12-15 mm in females; 13-16 mm in males). Based on the suspected phenotype, we screened subjects for the LMNA gene, for 8 sarcomeric genes, 5 desmosomal genes, and cardiac calcium, sodium and potassium channel disease genes. Results: Genetic analysis was completed in 37/49 athletes, 22 competitive and 27 non-competitive athletes, showing “borderline” clinical markers suggestive of hypertrophic cardiomyopathy (HCM,n. 24), dilated cardiomyopathy (n. 4), arrhythmogenic right ventricular dysplasia/cathecholaminergic polymorphic ventricular tachycardia (ARVD/CPVT, n. 11), long QT syndrome (LQTS, n. 4), sick sinus syndrome (SSS, n. 5), Brugada syndrome (BrS, n. 1). We identifyed 11 mutations in 9 athletes (an ARVD athlete was compound heterozygote for the PKP2 gene and an HCM athlete was double heterozygote for the MYBPC3 and TNNT2 genes): 3 known mutations related to LQTS, HCM and ARVD, respectively, and 8 novel mutations, located in the SCN5A, RyR2, PKP2, MYBPC3 and ACTC1 genes. The new mutations were absent in ~800 normal chromosomes and were predicted “probably damaging” by in silico analysis. Patch clamp analysis in channelopathies indicated for some mutation abnormal biophysical behavior of the corresponding mutant protein. Conclusion: Genetic analysis may help distinguish between physiology and pathology in athletes with clinically suspected heart disease

Selenotriapine – An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors

Triapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay

Gribov Problem for Gauge Theories: a Pedagogical Introduction

The functional-integral quantization of non-Abelian gauge theories is affected by the Gribov problem at non-perturbative level: the requirement of preserving the supplementary conditions under gauge transformations leads to a non-linear differential equation, and the various solutions of such a non-linear equation represent different gauge configurations known as Gribov copies. Their occurrence (lack of global cross-sections from the point of view of differential geometry) is called Gribov ambiguity, and is here presented within the framework of a global approach to quantum field theory. We first give a simple (standard) example for the SU(2) group and spherically symmetric potentials, then we discuss this phenomenon in general relativity, and recent developments, including lattice calculations.Comment: 24 pages, Revtex 4. In the revised version, a statement has been amended on page 11, and References 14, 16 and 27 have been improve