A decisão de exportar e o processo de seleção de mercados em grandes empresas

Diversos autores relacionam a regularidade das exportações de uma empresa com a forma pela qual foi tomada a decisão de exportar e com a estruturação do processo de seleção de mercados. Observando a lista das empresas brasileiras que exportam, ve-se que novos nomes aparecem enquanto que outros desaparecem. Entretanto, ha um conjunto de empresas que vem se mantendo como exportadores sistemáticos, aumentando ano a ano o seu volume exportado. Este estudo analisa o processo de decisão de exportar e de selegao de mercados em um conjunto de dez empresas selecionadas entre as que mais tern se destacado na atividade exportadora

Overview of Plasma Lens Experiments and Recent Results at SPARC_LAB

Beam injection and extraction from a plasma module is still one of the crucial aspects to solve in order to produce high quality electron beams with a plasma accelerator. Proper matching conditions require to focus the incoming high brightness beam down to few microns size and to capture a high divergent beam at the exit without loss of beam quality. Plasma-based lenses have proven to provide focusing gradients of the order of kT/m with radially symmetric focusing thus promising compact and affordable alternative to permanent magnets in the design of transport lines. In this paper an overview of recent experiments and future perspectives of plasma lenses is reported

Preimplantation Genetic Testing for Monogenic Kidney Disease

BACKGROUND AND OBJECTIVES: A genetic cause can be identified for an increasing number of pediatric and adult-onset kidney diseases. Preimplantation genetic testing (formerly known as preimplantation genetic diagnostics) is a reproductive technology that helps prospective parents to prevent passing on (a) disease-causing mutation(s) to their offspring. Here, we provide a clinical overview of 25 years of preimplantation genetic testing for monogenic kidney disease in The Netherlands. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective cohort study of couples counseled on preimplantation genetic testing for monogenic kidney disease in the national preimplantation genetic testing expert center (Maastricht University Medical Center+) from January 1995 to June 2019. Statistical analysis was performed through chi-squared tests. RESULTS: In total, 98 couples were counseled regarding preimplantation genetic testing, of whom 53% opted for preimplantation genetic testing. The most frequent indications for referral were autosomal dominant polycystic kidney disease (38%), Alport syndrome (26%), and autosomal recessive polycystic kidney disease (9%). Of couples with at least one preimplantation genetic testing cycle with oocyte retrieval, 65% experienced one or more live births of an unaffected child. Of couples counseled, 38% declined preimplantation genetic testing for various personal and technical reasons. CONCLUSIONS: Referrals, including for adult-onset disease, have increased steadily over the past decade. Though some couples decline preimplantation genetic testing, in the couples who proceed with at least one preimplantation genetic testing cycle, almost two thirds experienced at least one live birth rate

Propofol anesthesia improves stroke outcomes over isoflurane anesthesia—a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Background: It has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect the DNA dependent binding by interfering with the protein-DNA interface. However, how such small molecules affect the transcription factor-DNA interfaces and gene regulatory pathways through DNA structure distortion is not fully understood so far. Methodology/Principal Findings: In the present work, we have constructed some models, especially the ternary model of polyamides+DNA+GR DNA-binding domain (GRDBD) dimer, and carried out molecular dynamics simulations and free energy calculations for them to address how polyamide molecules disrupt the GRDBD and DNA interface when polyamide and protein bind at the same sites on opposite grooves of DNA. Conclusions/Significance: We found that the cyclic polyamide binding in minor groove of DNA can induce a large structural perturbation of DNA, i.e. a.4 A ˚ widening of the DNA minor groove and a compression of the major groove by more than 4A ˚ as compared with the DNA molecule in the GRDBD dimer+DNA complex. Further investigations for the ternary system of polyamides+DNA+GRDBD dimer and the binary system of allosteric DNA+GRDBD dimer revealed that the compression o

Watching the acetylene vinylidene intramolecular reaction in real time

It is a long-standing dream of scientists to capture the ultra-fast dynamics of molecular or chemical reactions in real time and to make a molecular movie. With free-electron lasers delivering extreme ultraviolet (XUV) light at unprecedented intensities, in combination with pump-probe schemes, it is now possible to visualize structural changes on the femtosecond time scale in photo-excited molecules. In hydrocarbons the absorption of a single photon may trigger the migration of a hydrogen atom within the molecule. Here, such a reaction was filmed in acetylene molecules (C2H2) showing a partial migration of one of the protons along the carbon backbone which is consistent with dynamics calculations on ab initio potential energy surfaces. Our approach opens attractive perspectives and potential applications for a large variety of XUV-induced ultra-fast phenomena in molecules relevant to physics, chemistry, and biology.Comment: 21 pages, 3 figures, submitte

Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism

BACKGROUND Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. METHODS Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. RESULTS Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. CONCLUSIONS These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease

The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

BACKGROUND: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. Methods: FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. High rates of FBP1 and FBP3 expression were observed in all cancer types. RESULTS: There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p<0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p<0.001 and 0.05 resp.), but not in bladder or prostate cancer. CONCLUSIONS: The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors

Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast. Revolutionary advances in contrast agent chemistry have delivered versatile angiogenesis-specific molecular MRI contrast agents. In this paper, we review recent advances in the preclinical application of paramagnetic and fluorescent liposomes for noninvasive visualization of the molecular processes involved in tumor angiogenesis. This liposomal contrast agent platform can be prepared with a high payload of contrast generating material, thereby facilitating its detection, and is equipped with one or more types of targeting ligands for binding to specific molecules expressed at the angiogenic site. Multimodal liposomes endowed with contrast material for complementary imaging technologies, e.g., MRI and optical, can be exploited to gain important preclinical insights into the mechanisms of binding and accumulation at angiogenic vascular endothelium and to corroborate the in vivo findings. Interestingly, liposomes can be designed to contain angiostatic therapeutics, allowing for image-supervised drug delivery and subsequent monitoring of therapeutic efficacy

Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization : an external validation study

We would like to thank the women who participated in the OPTIMIST study and the staff of the participating hospitals for their contributions to the OPTIMIST study.Peer reviewedPostprin