Miracle-dz/UniFAR-FTUs huggingface dataset:
Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

Significance Primary aldosteronism (PA) represents the most common adrenal disease and cause of secondary hypertension. However, little is known regarding adrenal cellular origins. Recently, subcapsular aldosterone-producing cell clusters (APCCs) were observed in normal adrenals. We hypothesize that APCCs are a contributor to PA. Here, we characterized the APCC transcriptome and show that CYP11B2 expression is increased compared with the rest of the adrenal cortex. We also show that many APCCs harbor known aldosterone-producing adenoma (APA)-related ion channels/pumps (ATPase, Na+/K+ transporting, α1-polypeptide and calcium channel, voltage-dependent, L-type, α1D-subunit) mutations that stimulate CYP11B2 expression and aldosterone production. Importantly, the mutation spectrum seen in APCCs differs from that reported for APA. These results provide molecular support for APCC as a precursor of PA. Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na+/K+ transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.
A readout circuit for wireless passive resonant-circuit sensors

This paper presents a readout circuit for wireless passive LC sensors, where the phase of the readout coil shows a small "dip" nearby the sensor's resonant frequency in the low-coupling-coefficient condition (a distance between the readout coil and the LC tank longer than 100 mm). To address this issue and enhance device sensitivity, in this study, a new symmetrical differential drive circuit was proposed where theoretical analysis and experimental verification were performed. The symmetrical differential drive circuit amplified the phase-dip at least 6 times when the scale factor between the reference inductor and the readout coil was 1.138. The proposed readout circuit was used to detect the variations of pressure with a 12 mm×12 mm×14 mm LC pressure sensor at an operational distance up to 100 mm between the LC sensor and the readout circuit, recording a measurement resolution lower than 0.4 kPa.
Cell mass and cell cycle dynamics of an asynchronous budding yeast population: Experimental observations, flow cytometry data analysis, and multi‐scale modeling

Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro‐environmental conditions. A major development in experimental single‐cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single‐cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi‐scale model (a population balance model [PBM] coupled to an unstructured model) and experimental data (both the overall physiology and cell size and cell cycle distributions) indicates that a mechanistic model is a suitable tool for describing the microbial population dynamics in a bioreactor. This study therefore contributes towards the understanding of the development of heterogeneous populations during microbial cultivations. More generally, it consists of a step towards a paradigm change in the study and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co‐existing single‐cell behaviors, rather than a unique response common to all cells in the cultivation. Biotechnol. Bioeng. 2013; 110: 812–826. © 2012 Wiley Periodicals, Inc.
Primitive cluster sensitive hashing for scalable content-based image retrieval in remote sensing archives

This paper proposes a novel unsupervised method based on primitive cluster sensitive hashing for fast and accurate image retrieval in large remote sensing (RS) archives. The proposed method consists of a three-steps algorithm. In the first step, each image in the archive is characterized by primitive clusters' descriptors. These descriptors are obtained through an unsupervised approach, which automatically extracts the image regions' descriptors and then associates them with primitive clusters. In the second step the primitive clusters' descriptors are transformed into multi-hash codes to represent each image. Then, in the last step, a multi-hash-code-matching scheme is applied to retrieve the images in the archive that are very similar to a query image. Experiments carried out on an archive of aerial images show that the proposed method provides distinctive multi-hash codes associated to the primitive clusters. Thus, it is more accurate than standard hashing methods, particularly under complex RS image retrieval tasks.
Satisfaction Level of New Mothers with Prenatal Care and the Healthcare Professionals Who Provide It.

INTRODUCTION Prenatal care is a key strategy to reduce maternal mortality. The aims of this work were to ascertain the level of satisfaction of new mothers with their pregnancy monitoring and with the medical professionals who provided prenatal care. SUBJECTS AND METHODS A descriptive study was conducted on 265 new mothers, 18-43 years of age, who had given birth at the Virgen de las Nieves University Hospital and the San Cecilio University Hospital in Granada (Spain) in April and May 2012. The data were collected with a questionnaire consisting of 28 items that elicited information from the subjects about their pregnancy, prenatal care activities, the healthcare professionals that provided the care, and those that they would like to monitor future pregnancies. There were also two open questions. The first was about the perceived needs of the participants and the second asked them to suggest ways that prenatal care could be improved. RESULTS The majority of the subjects (59.6%) had given birth for the first time. The midwife was the healthcare professional who performed most of the monitoring activities and resolved their doubts and problems (32.74%), gave the subjects tranquility and security (37.86%) and listened to their worries (34.53%). The subjects' satisfaction with the healthcare professionals was generally high. This was particularly true of the midwife (90.75%). Half of the subjects surveyed said that they wanted the midwife, obstetrician and general practitioner to monitor their pregnancy. They also underlined the need for longer and more visits with the midwife as well as more consultations with the obstetrician and higher number of ultrasounds. CONCLUSIONS The subjects were very satisfied with the work of the healthcare professionals that monitored their pregnancy, particularly with the midwife. However, they also highlighted expectations and needs that, if met, would increase their satisfaction.
Haemophilus ducreyi LspA Proteins Are Tyrosine Phosphorylated by Macrophage-Encoded Protein Tyrosine Kinases

ABSTRACT The LspA proteins (LspA1 and LspA2) of Haemophilus ducreyi are necessary for this pathogen to inhibit the phagocytic activity of macrophage cell lines, an event that can be correlated with a reduction in the level of active Src family protein tyrosine kinases (PTKs) in these eukaryotic cells. During studies investigating this inhibitory mechanism, it was discovered that the LspA proteins themselves were tyrosine phosphorylated after wild-type H. ducreyi cells were incubated with macrophages. LspA proteins in cell-free concentrated H. ducreyi culture supernatant fluid could also be tyrosine phosphorylated by macrophages. This ability to tyrosine phosphorylate the LspA proteins was not limited to immune cell lineages but could be accomplished by both HeLa and COS-7 cells. Kinase inhibitor studies with macrophages demonstrated that the Src family PTKs were required for this tyrosine phosphorylation activity. In silico methods and site-directed mutagenesis were used to identify EPIYG and EPVYA motifs in LspA1 that contained tyrosines that were targets for phosphorylation. A total of four tyrosines could be phosphorylated in LspA1, with LspA2 containing eight predicted tyrosine phosphorylation motifs. Purified LspA1 fusion proteins containing either the EPIYG or EPVYA motifs were shown to be phosphorylated by purified Src PTK in vitro. Macrophage lysates could also tyrosine phosphorylate the LspA proteins and an LspA1 fusion protein via a mechanism that was dependent on the presence of both divalent cations and ATP. Several motifs known to interact with or otherwise affect eukaryotic kinases were identified in the LspA proteins.
Implementation of type III controller for KY converter based on PSIM

The KY converter, which features fast transient response, non-pulsating output current and simple structure, is a novel step-up topology to overcome the disadvantages of the traditional boost converter. Therefore, in this paper, based on the method of state-space averaging, the KY converter, including the inductor copper resistance and the output capacitor resistance is analyzed and modeled as a small-signal ac circuit. After this, by selecting the type III compensator, which provides the required phase margin boost, and by determining the required crossover frequency based on the transient voltage spike and phase margin based on rule of thumb, the parameters of the type III compensator can be obtained. Finally, the effectiveness of the closed-loop load transient response of the KY converter is verified by the PSIM.
On methods for studying stochastic disease dynamics

Models that deal with the individual level of populations have shown the importance of stochasticity in ecology, epidemiology and evolution. An increasingly common approach to studying these models is through stochastic (event-driven) simulation. One striking disadvantage of this approach is the need for a large number of replicates to determine the range of expected behaviour. Here, for a class of stochastic models called Markov processes, we present results that overcome this difficulty and provide valuable insights, but which have been largely ignored by applied researchers. For these models, the so-called Kolmogorov forward equation (also called the ensemble or master equation) allows one to simultaneously consider the probability of each possible state occurring. Irrespective of the complexities and nonlinearities of population dynamics, this equation is linear and has a natural matrix formulation that provides many analytical insights into the behaviour of stochastic populations and allows rapid evaluation of process dynamics. Here, using epidemiological models as a template, these ensemble equations are explored and results are compared with traditional stochastic simulations. In addition, we describe further advantages of the matrix formulation of dynamics, providing simple exact methods for evaluating expected eradication (extinction) times of diseases, for comparing expected total costs of possible control programmes and for estimation of disease parameters.
The Voynich Manuscript is Written in Natural Language: The Pahlavi Hypothesis

The late medieval Voynich Manuscript (VM) has resisted decryption and was considered a meaningless hoax or an unsolvable cipher. Here, we provide evidence that the VM is written in natural language by establishing a relation of the Voynich alphabet and the Iranian Pahlavi script. Many of the Voynich characters are upside-down versions of their Pahlavi counterparts, which may be an effect of different writing directions. Other Voynich letters can be explained as ligatures or departures from Pahlavi with the intent to cope with known problems due to the stupendous ambiguity of Pahlavi text. While a translation of the VM text is not attempted here, we can confirm the Voynich-Pahlavi relation at the character level by the transcription of many words from the VM illustrations and from parts of the main text. Many of the transcribed words can be identified as terms from Zoroastrian cosmology which is in line with the use of Pahlavi script in Zoroastrian communities from medieval times.
Oldest known dinosaurian nesting site and reproductive biology of the Early Jurassic sauropodomorph Massospondylus

The extensive Early Jurassic continental strata of southern Africa have yielded an exceptional record of dinosaurs that includes scores of partial to complete skeletons of the sauropodomorph Massospondylus, ranging from embryos to large adults. In 1976 an incomplete egg clutch including in ovo embryos of this dinosaur, the oldest known example in the fossil record, was collected from a road-cut talus, but its exact provenance was uncertain. An excavation program at the site started in 2006 has yielded multiple in situ egg clutches, documenting the oldest known dinosaurian nesting site, predating other similar sites by more than 100 million years. The presence of numerous clutches of eggs, some of which contain embryonic remains, in at least four distinct horizons within a small area, provides the earliest known evidence of complex reproductive behavior including site fidelity and colonial nesting in a terrestrial vertebrate. Thus, fossil and sedimentological evidence from this nesting site provides empirical data on reproductive strategies in early dinosaurs. A temporally calibrated optimization of dinosaurian reproductive biology not only demonstrates the primary significance of the Massospondylus nesting site, but also provides additional insights into the initial stages of the evolutionary history of dinosaurs, including evidence that deposition of eggs in a tightly organized single layer in a nest evolved independently from brooding.
Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.

From 1 November 1992 through 1 May 1993 and from 1 November 1993 through 1 May 1994, we conducted a prospective surveillance study at the University of Texas M.D. Anderson Cancer Center (Houston) to evaluate the role of community respiratory virus infections in hospitalized adult bone marrow transplant (BMT) recipients, Respiratory secretions were obtained from all adult BMT recipients with acute respiratory illnesses. During these two winters, a community respiratory virus was isolated from 37 (36%) of 102 patients and 30 (26%) of 115 patients, respectively. Approximately half (49%) of these infections were due to respiratory syncytial virus (RSV); the remainder were due to influenza virus (18%), picornaviruses (18%), parainfluenza virus (9%), or adenovirus (6%). Fifty-eight percent of these infections were complicated by pneumonia, with an associated mortality of 51%. The pneumonias that complicated RSV infection were almost exclusively viral in origin and were associated with a mortality of 100% if not treated promptly with antiviral agents. In contrast, many of the pneumonias that complicated the other viral infections, such as influenza, appeared to be either self-limited viral pneumonias or secondary bacterial or fungal pneumonias. Community respiratory viruses are frequent causes of acute respiratory illnesses in adult BMT recipients hospitalized during the winter and are associated with substantial morbidity and mortality.
Regulation of Blood Flow in the Microcirculation

The regulation of blood flow has rich history of investigation and is exemplified in exercising skeletal muscle by a concerted interaction between striated muscle fibers and their microvascular supply. This review considers blood flow control in light of the regulation of capillary perfusion by and among terminal arterioles, the distribution of blood flow in arteriolar networks according to metabolic and hemodynamic feedback from active muscle fibers, and the balance between peak muscle blood flow and arterial blood pressure by sympathetic nerve activity. As metabolic demand increases, the locus of regulating oxygen delivery to muscle fibers “ascends” from terminal arterioles, through intermediate distributing arterioles, and into the proximal arterioles and feed arteries, which govern total flow into a muscle. At multiple levels, venules are positioned to provide feedback to nearby arterioles regarding the metabolic state of the tissue through the convection and production of vasodilator stimuli. Electrical signals initiated on smooth muscle and endothelial cells can travel rapidly for millimeters through cell‐to‐cell conduction via gap junction channels, rapidly coordinating vasodilator responses that govern the distribution and magnitude of blood flow to active muscle fibers. Sympathetic constriction of proximal arterioles and feed arteries can restrict functional hyperemia while dilation prevails in distal arterioles to promote oxygen extraction. With vasomotor tone reflecting myogenic contraction of smooth muscle cells modulated by flow‐induced vasodilator production by endothelium, the initiation of functional vasodilation and its modulation by shear stress and sympathetic innervation dictate how and where blood flow is distributed in microvascular networks. A remarkable ensemble of signaling pathways underlie the integration of smooth muscle and endothelial cell function in microvascular networks. These pathways are being defined with new insight as novel approaches are applied to understanding the cellular and molecular mechanisms of blood flow control.
Reducing PTSD symptoms through a gender norms and economic empowerment intervention to reduce intimate partner violence: a randomized controlled pilot study in Côte D'Ivoire

Background. Women living in war-affected contexts face high levels of gender-based violence, including intimate partner violence (Stark & Ager, 2011). Despite well-documented negative consequences, including posttraumatic stress disorder (PTSD) (Garcia-Moreno et al. 2006; Steel et al. 2009), evidence remains thin regarding intervention effectiveness to mitigate consequences in these settings. Methods. This study used a two-armed parallel pilot randomized controlled trial to compare the impact of a group savings only (control) to gender dialogue groups added to group savings (treatment) on women's symptoms of PTSD in northwestern Côte d'Ivoire. Eligible Ivorian women (18+ years, no prior experience with group savings) were invited to participate and 1198 were randomized into treatment groups. Results. In the ITT analyses, women in the treatment arm had significantly fewer PTSD symptoms relative to the control arm (β: −0.12; 95% CI: −0.20 to −0.03; p = 0.005). Partnered women in the treatment arm who had not experienced intimate partner violence (IPV) at baseline had significantly fewer PTSD symptoms than the control arm (β = −0.12; 95% CI: −0.21 to −0.03; p = 0.008), while those who had experienced IPV did not show significant differences between treatment and control arms (β = −0.09; 95% CI: −0.29 to 0.11; p = 0.40). Conclusions. Adding a couples gender discussion group to a women's savings group significantly reduced women's PTSD symptoms overall. Different patterns emerge for women who experienced IPV at baseline v. those who did not. More research is needed on interventions to improve mental health symptoms for women with and without IPV experiences in settings affected by conflict.
Polymer-Encapsulated Genetically Modified Cells Continue to Secrete Human Nerve Growth Factor for over One Year in Rat Ventricles: Behavioral and Anatomical Consequences

The long-term delivery of growth factors and other proteins into the CNS at putatively therapeutic yet safe levels continues to be technically constrained. In the present studies, the gene encoding human nerve growth factor (hNGF), introduced into a dihydrofolate reductase-based pNUT expression vector system, was engineered into a clonal baby hamster kidney (BHK) cell line. BHK-hNGF23 and mock-transfected cells were encapsulated in an immunoisolating polymeric device and transplanted into the lateral ventricles of healthy young adult rats for 13.5 months. As measured by ELISA, nanogram quantities of hNGF were released by encapsulated cells both prior to implantation (3.6 +/- 0.8 ng/device/24 h) and upon removal from rat lateral ventricles after 13.5 months in vivo (2.2 +/- 0.4 ng/ device/24 h). In addition, the hNGF released into the tissue culture medium was biologically active. Long-term encapsulated cell survival was confirmed by histologic analysis. The presence of genomic DNAs (hNGF transgene), as determined by PCR analyses, revealed that the transgene copy number from the recovered BHK-hNGF23 cells after 13.5 months in vivo was equivalent to preimplant levels. No deleterious effects from hNGF were detectable on body weight, mortality rate, motor/ambulatory function, or cognitive function as assessed with the Morris water maze and delayed matching to position in healthy young adult rats. In addition, there was no evidence that hNGF from these encapsulated cells produced hyperalgesia. Only tests of somatosensory thresholds revealed statistically significant effects related to the hNGF delivered in the present study, and that effect was limited to a decrease in the number of trials to asymptote. Animals receiving BHK-hNGF23 implants exhibited a marked hypertrophy of cholinergic neurons within the striatum (22% increase) and nucleus basalis (7% increase) but not the medial septum ipsilateral to the capsule. Moreover a robust sprouting of cholinergic fibers was observed within the frontal cortex and lateral septum proximal to the implant. These results indicate that encapsulated xenogeneic cells provide a safe and effective method for the long-term delivery of hNGF and potentially other neurotrophic factors within the CNS.