Letter from Geraldine Ferraro to an Aspiring Journalist in Italy

Letter from Geraldine Ferraro to an aspiring journalist in Italy.https://ir.lawnet.fordham.edu/vice_presidential_campaign_correspondence_1984_international/1338/thumbnail.jp

“Design and synthesis of novel heterocyclic compounds with potential biological activity”

The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. A wide number of N,N-dialkyl-(2-phenylindol-3-yl)glyoxylamides have been studied as potent and selective TSPO ligands exhibiting Ki values in the nanomolar/subnanomolar range, and stimulating steroid biosynthesis in rat C6 glioma cells to an extent similar to, or higher than that of classical TSPO ligands, such as PK 11195, Ro 5-4864 and alpidem. Starting from these derivatives, in this PhD work have been designed novel TSPO irreversible ligands bearing an electrophilic isothiocyanato group together with an irreversible NBD-fluorescent probe . The TSPO affinity of the new irreversible ligands was measured on rat tissue homogenates by [3H]Ro 5-4864 radiobinding kinetic assays, all compounds showing high affinities for the target protein. In addition with the aim to further refine the TSPO pharmacophore/topological model and to investigate the role of the 1-NH indole in the binding of these ligands to the TSPO, a novel series of N1-methylindole derivatives were synthesized. Within this series, the ligand N,N-di-n-propyl-(N1-methyl-2-(4’-nitrophenyl)indol-3yl)glyoxylamide ([11C]-29), featuring the best combination of affinity and lipophilicity, was labelled with carbon-11 for evaluation with positron emission tomography (PET) in monkey. After intravenous injection, [11C]-29 entered brain to give a high proportion of TSPO-specific binding. These findings augurs well for the future application of [11C]29 in humans. [11C]29 represents a promising new chemotypes for developing novel TSPO radioligands as biomarkers of neuroinflammation. Adenosine is a physiological nucleoside which plays an important role in many patho-physiological conditions in the central nervous system (CNS), as well as in peripheral organs and tissues through modulation of specific membrane G protein-coupled receptors (ARs), currently classified into A1, A2A, A2B, and A3 subtypes. A2A ARs occur mainly on neurons in the striatum and on cholinergic interneurons, but they are also found in the nucleus accumbens, olfactory tubercle, hippocampus and cerebral cortex. Recent evidences showed that A2A ARs may modulate a number of cellular processes affecting neuronal cell death in a broad spectrum of brain injury. A2A ARs resulted up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection. As this effect is exerted without observable peripheral effects, there is an increasing interest in the development of selective A2A AR antagonists as novel protective agents in neurodegenerative diseases. In recent years, we have described a series of 3-aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones (ATBIs) as potent adenosine receptors antagonists. In this PhD work, we have synthesized a novel series of ligands featuring modified substituents at the 10 position, combined with an appropriate aromatic ring at the 3-position. Synthesis, biological evaluation and structure-activity relationships for these new derivatives ATBI will be presented. Finally, the most promising A2A AR ATBI antagonist was evaluated for its neuroprotective effect on PC12 cells treated with dopamine neurotoxins: MPP+ or methamphetamine. We found a neuroprotective effect consisting of full prevention of neurotoxin-induced cell loss, as measured by combining a variety of staining techniques. These latter results, which were confirmed by combining neurotoxic models, each owing a different mechanism of action, offer a promising perspective for such a compound as a valuable tool to protect dopamine neurons

A estrutura a termo como previsor da atividade econômica real

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Sócio-Econômico. Economia.O objetivo deste trabalho é a analisar o poder de previsão da estrutura a termo da taxa de juros sobre o produto, investimento, gasto do governo, consumo das famílias, exportações, importações e IBC-BR. Será utilizada a análise de componentes principais para estimar os fatores nível, inclinação e curvatura da estrutura termo. O modelo estimado foi o de mínimos quadrados ordinários e o arcabouço usado para a análise dos dados estará relacionado principalmente aos mecanismos de transmissão da política monetária. O R2 ajustado de todos os modelos estimados foi consideravelmente alto. A curvatura foi determinante na estimação dos melhores modelos selecionados, apresentando significância em praticamente todos os modelos específicos. A inclinação teve significância em alguma defasagem apenas para o consumo das famílias, investimento e gasto do governo. Houve a evidência de um ciclo de juros de curto prazo para o produto, investimento, consumo das famílias, importações, e IBCB

Ethical Considerations in the Advent of 3D Printing Technology in Healthcare

The emergence of 3D printing technology in healthcare has ushered in a new era of personalized medical solutions. However, alongside its promises, this technology also introduces several critical challenges that demand attention. This research investigates the implications of 3D printing on patient safety, intellectual property, equity, data security, informed consent, and the roles of healthcare professionals. 3D printing has opened up remarkable opportunities in the creation of medical devices, implants, and prosthetics. Nevertheless, the potential for errors during the manufacturing process poses a significant concern. Ensuring the safety and reliability of 3D-printed medical products becomes paramount, as any defects or inaccuracies could have severe consequences on patient health and well-being. The accessibility of 3D printing technology raises apprehensions regarding intellectual property rights and regulatory standards. The possibility of replicating medical devices and pharmaceuticals may lead to patent infringements and pose difficulties in enforcing regulatory compliance. Striking a balance between innovation and protection of intellectual property becomes crucial in fostering a thriving 3D printing healthcare ecosystem. While 3D printing holds to democratize healthcare by offering personalized medical solutions, it also has the potential to exacerbate existing disparities in healthcare access. The cost of 3D printing technology and related services might prove prohibitive for certain communities, thereby widening the gap in access to advanced medical treatments. Addressing these disparities and ensuring equitable access to 3D printing healthcare solutions must be a priority for healthcare policymakers and stakeholders. The integration of 3D printing in healthcare necessitates the utilization and storage of sensitive patient data. However, ethical concerns emerge around the security and privacy of this data. Any breaches or misuse of patient information could not only compromise patient confidentiality but also erode trust in healthcare systems. Implementing robust data security measures and respecting patient privacy rights are essential to maintain public trust in 3D printing healthcare applications. As 3D printing enables the production of custom medical devices and implants, obtaining informed consent from patients becomes increasingly complex. Patients must comprehend the risks, benefits, and uncertainties associated with these personalized treatments to make autonomous decisions about their healthcare. Healthcare providers must develop comprehensive strategies to ensure adequate patient education and empowerment during the informed consent process

Pontos de corte para diagnóstico de sarcopenia em idosos a partir da força muscular de membros superiores e inferiores com ajustes alométricos

A presente tese defende a normalização da força e da massa muscular pelo tamanho corporal como estratégia eficiente para minimizar o viés das dimensões corporais sobre a funcionalidade de idosos. A tese foi composta de três objetivos específicos respondidos em quatro estudos originais. O primeiro objetivo foi propor expoentes alométricos para normalizar a força de membros superiores e inferiores pelo tamanho corporal e gerar pontos de corte para a fraqueza muscular de idosos, respondido em dois estudos originais. No Estudo I (Identification of muscle weakness in older adults from normalized upper and lower limbs strength: A cross-sectional study), que envolveu 94 idosos (IC 95%: 68,2 a 73,9 anos) de ambos os sexos, foram obtidas medidas de força muscular (preensão manual, extensão de joelhos dinâmica e isocinética), do tamanho corporal (antropometria, dimensões e índices) e mobilidade. Foram aplicadas estratégias de normalização (força/tamanho corporal) e alometria (força/tamanho corporalb; sendo b o expoente alométrico) associado à mobilidade dos idosos. Foram gerados 49 modelos válidos para identificar fraqueza muscular. A normalização aumentou a precisão dos pontos de corte em mulheres, mas não em homens. Todavia os ajustes nos homens também tornaram a força muscular independente do tamanho corporal, reduzindo o enviesamento para casos extremos. Isso implicou em menor risco de atribuir um diagnóstico falso-positiva/negativo à fraqueza muscular. E no Estudo II (Allometrically adjusted grip strength to identify low strength from 13,235 older adults of low- and middle-income countries), que envolveu idosos de ambos os sexos oriundos de seis países em desenvolvimento, a normalização da força muscular por dimensões corporais foi replicada em diferentes populações. Os métodos foram similares ao Estudo I, mas envolveu somente medidas da força de preensão manual, estatura e massa corporal. A relação não linear entre força e massa corporal foi confirmada, exceto para estatura. Os ajustes alométricos tornaram a força muscular independente do tamanho corporal e sua variabilidade destacou a necessidade de pontos de corte específicos para cada país. Os valores dos expoentes alométricos gerados para cada país foram muito próximos, confirmando a efetividade universal dessa estratégia. Nosso segundo objetivo foi aplicar comparativamente os expoentes alométricos propostos no Estudo I e outros relatados na literatura, a testar sua eficácia em normalizar a força e identificar fraqueza muscular. Assim, no Estudo III (Foreign allometric exponents adequately normalize isokinetic knee extension strength to identify muscle weakness and functional limitation in Portuguese older adults: A cross-sectional study) 132 idosos portugueses de ambos os sexos realizaram testes de mobilidade, força isocinética de extensão do joelho e medidas das dimensões corporais para normalizar a força (força/tamanho corporalb). Foram definidos pontos de corte para fraqueza muscular (curva ROC) a partir da força de extensão isocinética do joelho normalizada, ou não, identificado pelo menor quartil de mobilidade. Os pontos de corte da força absoluta, mostraram acurácia insuficiente (AUC<0.70). Expoentes alométricos, ainda que estrangeiros (três brasileiros e um norte americano), melhoraram a acurácia diagnóstica de fraqueza muscular. Concluímos que normalizar a força muscular isocinética de extensão do joelho, mesmo com o uso de expoentes alométricos estrangeiros é melhor do que nenhum ajuste. Nosso terceiro objetivo foi buscar uma estratégia simplificada para identificar a baixa massa muscular de idosos, baseada na limitação funcional para o risco de sarcopenia. Assim, para o Estudo IV (Normalizing Calf Circumference to identify low Skeletal Muscle Mass in Older Women: A Cross-sectional Study) foram propostos pontos de corte para o perímetro da panturrilha, normalizado pelo tamanho corporal, para identificar baixa massa muscular esquelética em mulheres idosas. Valores do perímetro da panturrilha de mulheres jovens (n=78) foram utilizados como referencia dos pontos de corte de baixa massa muscular (-2 desvio padrão). Os resultados mostraram que o perímetro da panturrilha normalizado pelo IMC identificou baixa massa muscular com maior acurácia do que os valores absolutos. A normalização retirou o costumeiro viés da relação de U invertido com a mobilidade (6MWT), geralmente observado em valores absolutos. A precisão obtida suportou o uso de PP·IMC-1 para identificar baixa massa muscular em mulheres idosas. Por conclusão, A estratégia alométrica proposta evita erros na classificação da baixa força muscular de idosos, decorrentes do viés causado pelo tamanho corporal. Possivelmente, isso reduz consideravelmente as chances de diagnósticos de casos falso positivos e negativos de sarcopenia em dimensões corporais de idosos com valores extremos. Palavras-chave: ajuste, alometricamente normalizado, avaliação, incapacidade, fragilidade, funcionalidade/estado funcional, medida, sarcopeniaThis thesis defends the normalization of strength and muscle mass by body size as an efficient strategy to minimize the bias of body dimensions on the functionality of the older adults. The thesis consisted of three specific objectives answered in four original studies. The first objective was to propose allometric exponents to normalize the strength of upper and lower limbs by body size and generate cutoff points for muscle weakness in the older adults, which was answered in two original studies. In Study I (Identification of muscle weakness in older adults from normalized upper and lower limbs strength: A cross-sectional study), which involved 94 older people (95% CI: 68.2 to 73.9 years) of both sexes, were muscle strength measurements were obtained (hand grip, dynamic and isokinetic knee extension), body size (anthropometry, dimensions, and indexes) and mobility. Strategies for normalization (strength/body size) and allometry (strength/body sizeb; b being the allometric exponent) associated with the mobility of the older adults were applied. Were generated 49 valid models to identify muscle weakness. Normalization increased the precision of the cut-off points in women but not in men. However, adjustments in men also made muscle strength independent of body size, reducing the bias for extreme cases. This implied a lower risk of attributing a falsepositive/ negative diagnosis to muscle weakness. And in Study II (Allometrically adjusted grip strength to identify low strength from 13,235 older adults of low- and middle-income countries), which involved older adults of both sexes from six developing countries, the normalization of muscle strength by body dimensions was replicated in different populations. The methods were like Study I, but only involved measurements of handgrip strength, height, and body mass. The non-linear relationship between strength and body mass was confirmed, except for height. Allometric adjustments made muscle strength independent of body size, and their variability highlighted the need for country-specific cutoff points. The values of allometric exponents generated for each country were very close to, confirming the universal effectiveness of this strategy. Our second objective was to comparatively apply the allometric exponents proposed in Study I and others reported in the literature, to test their effectiveness in normalizing strength and identifying muscle weakness. Thus, in Study III (Foreign allometric exponents suitably normalize isokinetic knee extension strength to identify muscle weakness and functional limitation in Portuguese older adults: A cross-sectional study) 132 Portuguese older adults of both genders performed tests of mobility, isokinetic strength of breast extension. knee and body dimension measurements to normalize strength (strength/body sizeb). Cutoff points for muscle weakness (ROC curve) were defined based on the normalized isokinetic knee extension strength, or not, identified by the lowest mobility quartile. The absolute strength cut-off points showed insufficient accuracy (AUC<0.70). Allometric exponents, although foreign (three Brazilians and one North American), improved the diagnostic accuracy of muscle weakness. We conclude that normalizing isokinetic knee extension muscle strength, even with the use of foreign allometric exponents, is better than no adjustment. Our third objective was to seek a simplified strategy to identify low muscle mass during aging, based on functional limitation for the risk of sarcopenia. Thus, for Study IV (Normalizing Calf Circumference to identify low Skeletal Muscle Mass in Older Women: A Cross-sectional Study) cut-off points were proposed for the calf perimeter, normalized by body size, to identify low skeletal muscle mass in older women. Calf circumference values for young women (n=78) were used as a reference for low muscle mass cutoff points (-2 standard deviation). The results showed that the calf perimeter normalized by BMI identified low muscle mass with greater accuracy than the absolute values. Normalization removed the usual bias of the inverted U-to-mobility ratio (6MWT), usually seen in absolute values. The accuracy obtained supported the use of PP·BMI-1 to identify low muscle mass in older women. In conclusion, the proposed allometric strategy avoids errors in the classification of low muscle strength in the older adults, resulting from the bias caused by body size. Possibly, this considerably reduces the chances of diagnosing false positive and negative cases of sarcopenia in body dimensions of older people with extreme values

Induction of Somatic Embryogenesis in Plants: Different Players and Focus on WUSCHEL and WUS-RELATED HOMEOBOX (WOX) Transcription Factors

In plants, other cells can express totipotency in addition to the zygote, thus resulting in embryo differentiation; this appears evident in apomictic and epiphyllous plants. According to Haberlandt's theory, all plant cells can regenerate a complete plant if the nucleus and the membrane system are intact. In fact, under in vitro conditions, ectopic embryos and adventitious shoots can develop from many organs of the mature plant body. We are beginning to understand how determination processes are regulated and how cell specialization occurs. However, we still need to unravel the mechanisms whereby a cell interprets its position, decides its fate, and communicates it to others. The induction of somatic embryogenesis might be based on a plant growth regulator signal (auxin) to determine an appropriate cellular environment and other factors, including stress and ectopic expression of embryo or meristem identity transcription factors (TFs). Still, we are far from having a complete view of the regulatory genes, their target genes, and their action hierarchy. As in animals, epigenetic reprogramming also plays an essential role in re-establishing the competence of differentiated cells to undergo somatic embryogenesis. Herein, we describe the functions of WUSCHEL-RELATED HOMEOBOX (WOX) transcription factors in regulating the differentiation-dedifferentiation cell process and in the developmental phase of in vitro regenerated adventitious structures

Erinea in the 'Ansonica' grapevine cultivar: trichome complement, histological effects and analysis of chlorophyll fluorescence in affected leaves

Grapevine leaves are usually characterized by trichomes, specialized epidermal cells. They are interesting in ampelography and also important for the plant ecological responses in biotic and abiotic interactions. In nature, the trichome development is a genetic trait but it can be modified by pests as eriophyid mites. Colomerus vitis is quite common and its economic value is sometime substantial. Here, we studied the leaf erineum induced by C. vitis on 'Ansonica' ('Inzolia'), an important grapevine cultivar characterized by a low level of leaf trichome coating. To date, the interaction between C. vitis and grape has been investigated in few pedo-climatic conditions and no data are reported in 'Ansonica'. Therefore, our objectives were: (1) the analysis, in a Tuscan environment, of the morphology and histology of trichomes in 'Ansonica' leaves unaffected or affected by C. vitis; (2) evaluation, in mature leaves, of the effects of the mite both on pigment content and chlorophyll a fluorescence parameters. 'Ansonica' was devoid of glandular trichomes but it has been established the presence of few simple trichomes strictly associated with the veins. In the erineal sectors, a dense proliferation of simple trichomes in the abaxial epidermis and the development of hyperplasia in the adaxial surface were observed. Moreover, the leaf sections in the erineal regions were thicker due to an abnormal development of the lacunar parenchyma, and trichome proliferation was also extended to interveinal regions. Leaves with erinea showed a deficient content of carotenoids, in comparison to unaffected leaves. In 'Ansonica' leaves, C. vitis induced a decrease in the steady-state operational efficiency of photosystem II associated to a reduction in photochemical quenching and an increase in non-photochemical quenching values. In leaves with erinea, the reduction of photosystem II efficiency was extended to foliar areas not directly affected by galls. The collected results highlight that 'Ansonica' is susceptible to attacks by C. vitis and in the case of widespread leaf attacks the productive damage should not be underestimated

Molecular aspects of zygotic embryogenesis in sunflower (Helianthus annuus L.): correlation of positive histone marks with HaWUS expression and putative link HaWUS/HaL1L

Main conclusion The link HaWUS/HaL1L, the opposite transcriptional behavior, and the decrease/increase in positive histone marks bond to both genes suggest an inhibitory effect of WUS on HaL1L in sunflower zygotic embryos. In Arabidopsis, a group of transcription factors implicated in the earliest events of embryogenesis is the WUSCHELRELATED HOMEOBOX (WOX) protein family including WUSCHEL (WUS) and other 14 WOX protein, some of which contain a conserved WUS-box domain in addition to the homeodomain. WUS transcripts appear very early in embryogenesis, at the 16-cell embryo stage, but gradually become restricted to the center of the developing shoot apical meristem (SAM) primordium and continues to be expressed in cells of the niche/organizing center of SAM and floral meristems to maintain stem cell population. Moreover, WUS has decisive roles in the embryonic program presumably promoting the vegetative-to-embryonic transition and/or maintaining the identity of the embryonic stem cells. However, data on the direct interaction between WUS and key genes for seed development (as LEC1 and L1L) are not collected. The novelty of this report consists in the characterization of Helianthus annuus WUS (HaWUS) gene and in its analysis regarding the pattern of the methylated lysine 4 (K4) of the Histone H3 and of the acetylated histone H3 during the zygotic embryo development. Also, a parallel investigation was performed for HaL1L gene since two copies of the WUS-binding site (WUSATA), previously identified on HaL1L nucleotide sequence, were able to be bound by the HaWUS recombinant protein suggesting a not described effect of HaWUS on HaL1L transcription