Miracle-dz/UniFAR-FTUs huggingface dataset:
Several Types of Somatic Mutations Induce Autonomous Production of Aldosterone in Primary Aldosteronism

We detected a low CYP17/HSD3B2 ratio in APA tissue, indicating that the cortisol pathway is suppressed in APA and also observed a high CYP11B2/CYP11B1 ratio in APA tissue, suggesting that the aldosterone pathway is accelerated in APA [8]. Furthermore, we reported that there were no KCNJ5 gene mutations in the normal tissue adhering to KCNJ5 gene mutationharboring APA, suggesting that somatic mutations of the KCNJ5 gene only occur in APA tissue [9]. On the other hand, we had clearly demonstrated that APA cells produce markedly less cortisol than normal adrenal cells, and it is suggested that KCNJ5 gene mutations dominantly induce the aldosterone production pathway as well as a concomitant decline in cortisol production, resulting in highly autonomous aldosterone production [9]. It is possible to consider that accelerated aldosterone production in APA is caused mainly by channelopathies, as reported by Gomez-Sanchez CE [4]. Those channelopathies may increase calcium entry inside adrenal cells, activating Ca-dependent intracellular signaling systems related to regulating aldosterone synthesis. Then we have questions how to treat the patients with PA possessing those channelopathies, to do surgery or not? We should perform adrenal vein sampling (AVS) before surgical treatment because of precise detection of unilateral adrenal lesions, while AVS cannot always be done for all patients with PA because of inadequate numbers of AVS-radiologists. Is it possible to use calcium channel blockade for medical treatment? Moreover, selective CYP11B2 inhibitors have recently been reported, which could be promising drug candidates for the treatment of aldosterone related diseases [10-12]. Then, new treatment, such as local injection of specific CYP11B2 inhibitors should also be considered for adrenal lesions that cause hyperaldosteronism. Moreover, we should precisely evaluate the long-term efficacy of MR antagonists for hyperaldosteronism[13].
USING EARSKETCH TO BROADEN PARTICIPATION IN COMPUTING AND MUSIC

EarSketch is a STEAM learning intervention that combines a programming environment and API for Python and JavaScript, a digital audio workstation, an audio loop library, and a standards-aligned curriculum to teach introductory computer science together with music technology and composition. It seeks to address the imbalance in contemporary society between participation in music-making and music-listening activities and a parallel imbalance between computer usage and computer programming. It also seeks to engage a diverse population of students in an effort to address long-standing issues with underrepresentation — particularly of women — in both computing and music composition. This paper summarizes the design of the EarSketch curriculum and learning environment and its deployment contexts to date, along with key findings from a pilot study. It builds upon prior publications by contextualizing the project’s motivations and interpreting its findings in the dual realms of participation in computer science and in music creation.
Classical and Molecular Cytogenetics of the Panther Genet Genetta maculata (Mammalia, Carnivora, Viverridae)

Genets (Genetta) are a genus of African mammalian carnivorans with 14 currently recognized species, although taxonomic uncertainties remain, particularly regarding the number of species within the large-spotted genet complex. This study presents the first banded karyotype and molecular cytogenetic analysis of a genetically identified panther genet, Genetta maculata, the most common and widespread taxon of the large-spotted genet complex, with a wide distribution in sub-Saharan Africa. Sampled in Gauteng Province, South Africa, it could be assigned to the subspecies G. m. letabae on geographic grounds and had a similar karyotype (2n = 52, FNa = 96) to those published for a panther genet from Ethiopia and for the West African large-spotted genet G. pardina. Notably, the specimen had a different autosomal morphology (2 acrocentric chromosomes) from that previously attributed to letabae (a single acrocentric chromosome), but the latter assignment was uncertain because the studied individuals were captive born and assigned based solely on a presumed origin in the former Transvaal Province of South Africa. Fluorescence in situ hybridization with a telomere repeat probe revealed the presence of telomeric sequences in the centromeres of most chromosomes, the so-called interstitial telomeric sites (ITSs). Since genets seem to have a unique, highly rearranged karyotype among feliforms and relatively low interspecific karyotypic variation, and considering the known instability of ITSs, we suggest that the large amount of ITSs found here might be due to evolutionarily recent extensive genomic rearrangements. This study provides cytogenetic information that contributes to our understanding of chromosomal variation and genomic rearrangements in genets, and valuable baseline data for future studies of karyotype evolution in carnivores in general and viverrids in particular.
Systematic Analysis of the Photocurrent Spectroscopy on InGaN/GaN Blue Light-Emitting Diodes

We demonstrate a method of systematic analysis for the photocurrent spectroscopy on InGaN/GaN light-emitting diodes (LEDs). By normalizing photocurrent data at a photon energy of 3.2 eV for blue LEDs, we show that accurate comparison of active quantum wells is possible. Bias-dependent photocurrent measurements reveal that there are fixed points in photocurrent data from which an effective bandgap energy can be determined. The method presented in this paper can be useful when one needs to compare the LEDs fabricated at different times or by different processes.
Antioxidant activity of carvedilol in cardiovascular disease

Oxidative and inflammatory stresses are cardinal in the pathogenesis of hypertension and atherosclerosis. Oxidative stress also leads to the induction of inflammation through the activation of proinflammatory transcription factors. Understanding the mechanisms leading to oxidative stress and the means of suppressing it are important in controlling complications related to atherogenesis, since oxidative and inflammatory stress are important in the pathogenesis of atherosclerosis. The failure of chemical antioxidants [which scavenge reactive oxygen species (ROS)], such as vitamins E and C, has led to further exploration of the ROS-suppressive effects of drugs used in the treatment of cardiovascular disease. Carvedilol has been shown to possess both ROS-scavenging and ROS-suppressive effects, and its use is associated with a reduction in oxidative stress. Furthermore, anti-inflammatory effects of carvedilol have now been described. Although further clinical investigations are required, these properties may contribute to the improvement in clinical outcomes observed with carvedilol.
Extending Top-Down Mass Spectrometry to Proteins with Masses Greater Than 200 Kilodaltons

For characterization of sequence and posttranslational modifications, molecular and fragment ion mass data from ionizing and dissociating a protein in the mass spectrometer are far more specific than are masses of peptides from the protein's digestion. We extend the ∼500-residue, ∼50-kilodalton (kD) dissociation limitation of this top-down methodology by using electrospray additives, heated vaporization, and separate noncovalent and covalent bond dissociation. This process can cleave 287 interresidue bonds in the termini of a 1314-residue (144-kD) protein, specify previously unidentified disulfide bonds between 8 of 27 cysteines in a 1714-residue (200-kD) protein, and correct sequence predictions in two proteins, one with 2153 residues (229 kD).
Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.
Photoactivation of Vascular iNOS and Elevation of cGMP In Vivo: Possible Mechanism for Photovasorelaxation and Inhibition of Restenosis in an Atherosclerotic Rabbit Model ¶

Recently, intravascular low‐power red laser light (LPRLL) therapy has been proposed for the prevention of postangioplasty restenosis due to the observed inhibition of experimental neointimal formation. The objective of this study was to determine the impact of endoluminal LPRLL on vascular levels of inducible nitric oxide synthase (iNOS) and cyclic guanosine monophosphate (cGMP) to help define the mechanism of this effect. Eight atherosclerotic male adult New Zealand White rabbits weighing 4–6 kg were used in these studies. The iliac arteries were treated in separate zones with: (1) balloon inflation only; (2) laser illumination only; and (3) balloon inflation + laser illumination. An uninjured zone of the iliac artery served as a control. Laser irradiation (630 nm) was delivered to the vessel wall via a Cold™ laser Illuminator (Cook, Inc., Bloomington, IN), with a 3 mm–diameter balloon. Experiments demonstrated that vascular cGMP levels obtained immediately following treatment in the balloon only group was the lowest (0.29 ± 0.05 pmol/mg protein) and significantly lower compared with the uninjured controls (1.01 ± 0.07 pmol/mg protein) (P < 0.001). In the laser only treated group cGMP levels were significantly increased (2.87 ± 0.12 pmol/mg protein) compared with the uninjured control (P < 0.001) and the balloon only group (P < 0.001). Vascular cGMP levels in the balloon + laser group (2.09 ± 0.07 pmol/mg protein) was also increased compared to the balloon only (P < 0.001) and control (P < 0.001) groups. Qualitative analysis of Western blot demonstrated that laser illumination induces iNOS. In contrast balloon dilatation did not induce iNOS. Balloon + laser treatment, however, tended to restore the expression of iNOS. Our study demonstrated that intravascular low dose laser irradiation induces iNOS and elevates vascular cGMP in an in vivo atherosclerotic rabbit model.
Gnotobiotic Mouse Immune Response Induced by Bifidobacterium sp. Strains Isolated from Infants

ABSTRACT Bifidobacterium, which is a dominant genus in infants’ fecal flora and can be used as a probiotic, has shown beneficial effects in various pathologies, including allergic diseases, but its role in immunity has so far been little known. Numerous studies have shown the crucial role of the initial intestinal colonization in the development of the intestinal immune system, and bifidobacteria could play a major role in this process. For a better understanding of the effect of Bifidobacterium on the immune system, we aimed at determining the impact of Bifidobacterium on the T-helper 1 (TH1)/TH2 balance by using gnotobiotic mice. Germfree mice were inoculated with Bifidobacterium longum NCC2705, whose genome is sequenced, and with nine Bifidobacterium strains isolated from infants’ fecal flora. Five days after inoculation, mice were killed. Transforming growth factor β1 (TGF-β1), interleukin-4 (IL-4), IL-10, and gamma interferon (IFN-γ) gene expressions in the ileum and IFN-γ, tumor necrosis factor alpha (TNF-α), IL-10, IL-4, and IL-5 secretions by splenocytes cultivated for 48 h with concanavalin A were quantified. Two Bifidobacterium species had no effect (B. adolescentis) or little effect (B. breve) on the immune system. Bifidobacterium bifidum, Bifidobacterium dentium, and one B. longum strain induced TH1 and TH2 cytokines at the systemic and intestinal levels. One B. longum strain induced a TH2 orientation with high levels of IL-4 and IL-10, both secreted by splenocytes, and of TGF-β gene expression in the ileum. The other two strains induced TH1 orientations with high levels of IFN-γ and TNF-α splenocyte secretions. Bifidobacterium's capacity to stimulate immunity is species specific, but its influence on the orientation of the immune system is strain specific.
Test of Endogenous Growth Theory via Technological Spillover Effects of International Capital Good Flows

This paper aims to test endogenous growth models based on technology spillovers. So far similar models have tested the effects of total physical capital formation and international capital goods flows on long-run economic growth. We exploited VAR models and explored that imported machinery and equipment has no long-run growth effects. However, in the short-run, growth effects appeared in most of the impulse responses. Since the impulse response values of some countries go apart from the steady-state growth rate in the longrun, we hypothesized that like economies absorption, diffusion and physical capital-human capital complementarity, market imperfections facts must be incorporated in the models to understand the long-run economic growth.
Analyzing Public Expenditure Benefit Incidence in Health Care: Evidence from India

The effectiveness of public spending remains a relatively elusive empirical issue. This preliminary analysis is an attempt, using benefit incidence methodology, to define the effectiveness of spending at the subnational government level in India’s health sector. The results reveal that the public health system is “seemingly” more equitable in a few states, while regressivity in the pattern of public health-care utilization is observed in others. Both results are to be considered with caution, as the underdeveloped market for private inpatient care in some states might be a factor in the disproportionate crowding-in of inpatients, making the public health-care system simply appear more equitable. However, patients “voting with their feet” and choosing better, private services seems evident only in the higher-income quintiles. Results also suggest that polarization is distinctly evident in the public provisioning of health-care services, though more related to inpatient, rather than ambulatory, services.
Control of an artificial-hip-joint simulator to evaluate dislocation

Total hip arthroplasty (THA) is performed to replace all or part of a human hip joint with an artificial joint for patients who have rheumatoid arthritis or osteoarthritis of the hip joint. Although THA might result in postoperative complications of dislocation, wear and/or loose, their mechanisms have not been analyzed enough. We have developed an artificial-hip-joint simulator that can generate the same joint posture and joint contact force as those in daily life motion in order to evaluate the performance of the artificial-hip-joint. Dislocation of the artificial-hip-joint during daily living activities was generated by the simulator in order to analyze its mechanism.
Is warfarin the right anticoagulant in idiopathic pulmonary fibrosis?

We have with great interest read the article by Noth and colleagues from The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet) in a recent issue of the Journal. They report on the results from the Placebo-Controlled Randomized Trial of Warfarin in IPF (ACE-IPF) (1). The ACE-IPF study was aborted before study endpoint due to a low probability of benefit and an increase in mortality in the warfarintreated subjects (14 warfarin vs. 3 placebo deaths; P 1⁄4 0.005). We compliment the researchers for a well-conducted study, but at the same time we caution the idiopathic pulmonary fibrosis (IPF) community not to abandon the principle of anticoagulation in IPF solely due to the results from the present study. Besides coumarins, there are other anticoagulant agents, and among these, unfractionated and low-molecular-weight heparins are the most commonly used anticoagulant and antithrombotic agents. In the only other clinical trial with anticoagulation, a combination of warfarin, prednisolone, and heparin showed that systemic anticoagulant therapy may have a beneficial effect on survival in patients with IPF (2). Many of the pathways that are involved in fibrogenesis in IPF are unknown, but the initial event involves alveolar epithelial injury; the mechanisms of lung injury and fibrogenesis have been explored by the use of animal models, and increased procoagulant activity (tissue factor/VIIa) as well as suppression of the normal fibrinolytic activity through up-regulation of several protease inhibitors in the alveoli seems of great importance (3). The same mechanisms have been observed in patients with IPF, acute lung injury, and sarcoidosis, and thus anticoagulation might be beneficial in IPF as summarized in References 1 and 3. However, in addition to their well-known anticoagulant effects, heparins have documented antiinflammatory and antifibrotic properties, as shown in multiple laboratory, animal, and human studies (4). Normally, heparin and low-molecular-weight heparin are administered either intravenously or subcutaneously, which very likely will represent a barrier for self-administration for many patients. However, several studies have investigated the intrapulmonary route, and studies have also proven antiinflammatory effects after inhalation of heparin (5). Inhaled heparin has been shown to be safe in both healthy volunteers and patients with IPF with respect to pulmonary function, gas exchange, exercise capacity, and local and systemic anticoagulant effects (3, 6). Therefore, based on the multiple antiinflammatory and antifibrotic effects of heparin, the encouraging results from Kuno and colleagues, and the disappointing results from Noth and coworkers, we question the choice of anticoagulant drug (warfarin) for treatment of IPF and suggest that studies with inhaled heparin should be prosecuted in the future.
Isoflurane prevents learning deficiencies caused by brief hypoxia and hypotension in adult Sprague Dawley rats

Abstract Context: Hypotension causes histologic changes in the hippocampal CA1 area, while behavior remains unchanged. We believe that an even stronger insult may also cause behavioral changes. Objective: We used a rat hemorrhagic shock model plus temporary hypoxia to assess functional outcome at different time points post-injury. Our hypothesis is that the damage can be attenuated by the use of isoflurane. Materials and methods: Rats were subjected to brief hypotension. Animals were evaluated at different time points after receiving hypoxia and hypotension, with and without isoflurane treatment. Results: The administration of isoflurane after the insult protected the animals from memory alterations. No histopatologic changes were found in any of the groups. Discussion and conclusions: This observation suggests that in this model of hypotension plus hypoxia there is mild cerebral damage that is reflected by memory changes. Exposure to isoflurane after the insult can prevent the onset of memory deficits.
Microscopic Modeling of HfOx RRAM Operations: From Forming to Switching

We propose a model describing the operations of hafnium oxide-based resistive random access memory (RRAM) devices at the microscopic level. Charge carrier and ion transport are self-consistently described starting from the leakage current in pristine HfO2. Material structural modifications occurring during the RRAM operations, such as conductive filament (CF) creation and disruption, are accounted for. The model describes the complex processes leading to a formation of the CF and its dependence on both electrical conditions (e.g., current compliance, voltage stress, and temperature) and device characteristics (e.g., electrodes material and dielectric thickness).
Diaries for Recovery From Critical Illness.

NURSING IMPLICATIONS During a patient’s admission to the ICU, they can experience extreme physical and psychological stressors. These experiences impact on their recovery from critical illness andmay result in both physical and psychological disorders. One strategy that has been developed and implemented by clinical staff to treat the psychological distress prevalent in ICU survivors is the use of patient diaries. These provide a background to the cause of the patient’s ICU admission and an ongoing narrative outlining day-to-day activities. Approximately 20 million patients require treatment in ICUs worldwide. The combined after-effects of critical illness and the ICU experience have been linked to both shortand long-term psychological compromise. These can have a significant impact on the patient’s psychological and physical recovery. Therefore, patient diaries have been developed in an effort to address physical and psychological function, as well as consider the long-term implications on the patient and their families.
Information security: management's effect on culture and policy

Purpose – This study proposes to put forward and test a theoretical model that demonstrates the influence of top management support on an organization's security culture and level of security policy enforcement.Design/methodology/approach – The project used a combination of qualitative and quantitative techniques. The grounded theory approach was used to analyze responses to open‐ended questions answered by 220 certified information system security professionals. Using these responses, a survey instrument was developed. Survey results were analyzed using structural equation modeling.Findings – Evidence suggests that top management support is a significant predictor of an organization's security culture and level of policy enforcement.Research limitations/implications – During instrument validation, a special effort removed survey items that appeared overly intrusive to the respondents. In this endeavor, an expert panel of security practitioners evaluated all candidate items on a willingness‐to‐answer scal.