Miracle-dz/UniFAR-FTUs huggingface dataset:
Relative contributions of endothelial, inducible, and neuronal NOS to tone in the murine pulmonary circulation.

Nitric oxide plays an important role in modulating pulmonary vascular tone. All three isoforms of nitric oxide synthase (NOS), neuronal (nNOS, NOS I), inducible (iNOS, NOS II), and endothelial (eNOS, NOS III), are expressed in the lung. Recent reports have suggested an important role for eNOS in the modulation of pulmonary vascular tone chronically; however, the relative contribution of the three isoforms to acute modulation of pulmonary vascular tone is uncertain. We therefore tested the effect of targeted disruption of each isoform on pulmonary vascular reactivity in transgenic mice. Isolated perfused mouse lungs were used to evaluate the effect of selective loss of pulmonary nNOS, iNOS, and eNOS with respect to hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent and -independent vasodilation. eNOS null mice had augmented HPV (225 ± 65% control, P < 0.02, mean ± SE) and absent endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was preserved. HPV was minimally elevated in iNOS null mice and normal in nNOS null mice. Both nNOS and iNOS null mice had normal endothelium-dependent vasodilation. In wild-type lungs, nonselective NOS inhibition doubled HPV, whereas selective iNOS inhibition had no detectable effect. In intact, lightly sedated mice, right ventricular systolic pressure was elevated in eNOS-deficient (42.3 ± 1.2 mmHg, P< 0.001) and, to a lesser extent, in iNOS-deficient (37.2 ± 0.8 mmHg, P < 0.001) mice, whereas it was normal in nNOS-deficient mice (30.9 ± 0.7 mmHg, P = not significant) compared with wild-type controls (31.3 ± 0.7 mmHg). We conclude that in the normal murine pulmonary circulation 1) nNOS does not modulate tone, 2) eNOS-derived nitric oxide is the principle mediator of endothelium-dependent vasodilation in the pulmonary circulation, and 3) both eNOS and iNOS play a role in modulating basal tone chronically.
Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice*

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2NI) and R531G (AMPKγ2RG), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2NI or AMPKγ2RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2NI or AMPKγ2RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2NI and AMPKγ2RG, respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2NI or AMPKγ2RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2WT mice, AMPKγ2NI and AMPKγ2RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2RG but not AMPKγ2NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2NI and AMPKγ2RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD.
Performances of a turbocharged E100 engine with direct injection and variable valve actuation

Current flexi fuel gasoline and ethanol engines have brake efficiencies generally lower than a dedicated gasoline engines because of the constraints to accommodate a variable mixture of the two fuels. Considering ethanol has a few advantages with reference to gasoline, namely the higher octane number and the larger heat of vaporization, the paper explores the potentials of dedicated pure ethanol engines using the most advanced techniques available for gasoline engines, specifically direct injection, turbo charging and variable valve actuation. Computations are performed with state-of-the-art, well validated, engine and vehicle performance simulations packages, generally accepted to produce accurate results targeting major trends in engine developments. The higher compression ratio and the higher boost permitted by ethanol allows larger top brake efficiencies than gasoline, while variable valve actuation produces small penalties in efficiency changing the load. Finally, small, high power density, turbo charged, direct injection, variable valve actuation load controlled engines are proved to operate very efficiently over driving cycles.
Prediction of osteoporosis using dental radiographs and age in females

Aims and Objectives: To evaluate the role of dental radiograph as a screening tool for diagnosis of osteoporosis in females. Materials and Methods: In the present study, 50 women between the age group of 40-60 were recruited, and patients with systemic disorder and taking calcium supplements, and women who are not willing for investigation were excluded. Their detailed medical history was obtained and dental radiographs were made, bone mineral density was measured at left radial bone using ultrasound. The radiographs were subjected to image analysis method using manual tracing of gonial angle, antegonial angle, antegonial depth, antegonial index, mental index and mandibular cortical index. Statistical discrimination analysis was applied to predict the presence of osteoporosis. With use of these indices, the sensitivity and specificity of orthopantomograph (OPG) radiograph to assess age-related changes in bone were compared. Radiomorphometric indices (RMI) were also scrutinized to depict the sensitivity and specificity of each index in the prediction of osteoporosis. Results: Study results showed no significant differences between bone mineral density (BMD) and radiomorphometric analysis in the diagnoses of osteoporotic females. Out of 29, diagnosed as osteoporotic by radiograph 23 were confirmed by BMD and six were diagnosed as osteopenic. Among the six indices used, AGA and AGD showed more reproducible results. Conclusion: With our study results, we come to an arrival that OPG radiographs show overall sensitivity of 0.75 or 75% and specificity of 0.81 or 81% in the diagnosis of osteoporosis, and that anti gonial angle (AGA) and anti gonial depth (AGD) are the most reliable indices. Hence, we conclude that panoramic-based RMI can be used as an ancillary method in the diagnosis of osteoporosis.
MEDICATION HISTORY DOCUMENTATION IN REFERRAL LETTERS OF CHILDREN PRESENTING AT THE EMERGENCY UNIT OF A TEACHING HOSPITAL IN LAGOS, NIGERIA

Background: Medical literature has demonstrated that referral hospitals often receive inadequate information about the care and medications their patients received from referring hospitals. Objective: This study aimed to assess the completeness of referral letters, especially the medication history, for patient presenting at the children emergency room of a teaching hospital in Lagos, Nigeria. Method: A pro forma form was developed to obtain from the referral letters the demographic information of children referred to the emergency room of the Lagos University Teaching Hospital (LUTH), Idiaraba, over a period of three months. The nature of the referring centre, tentative diagnoses made at the referring centre, duration of illness prior to referral, vital signs and physical examination findings, investigation results, and treatment given were also extracted from the letters. In addition, we extracted from the letters the name, dosage, frequency and duration of use of medicines administered at the referring centres. Parents were also interviewed about the details of medicines used prior to presentation of their child at the referring centres. Results: Among those referred with a letter, 100 patients met the inclusion criteria and constituted those evaluated in this study. Most of the patients were referred from general hospitals (31%), another tertiary hospital (29%), and private hospitals/clinics (24%). Gender (30%) and tentative diagnoses (12%) were omitted in the referral letters. However, information about the weight (82%), vital signs (57%), physical examination findings (44%), treatment given (92%), and medication history (71%) were much more omitted in the referral letters. Conclusion: Medication history as well as many other data points is infrequently reported in referral letters to a tertiary care hospital in Lagos, Nigeria. Standard referral guidelines may be useful to improve documentation of medication history.
Long-Term Outcome of Second-Line Antiretroviral Therapy in Resource-Limited Settings

There is limited information on efficacy and durability of second-line antiretroviral therapy (2NL) beyond 12 months in resource-limited settings. A total of 73 patients were enrolled into a prospective 2NL observational cohort in Nigeria. Second-line antiretroviral therapy consisted of lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors. Time on 2NL ranged from 15 to 31 months. Genotypes were retrospectively done and not available to guide second-line regimen choice. At enrollment, median CD4 count was 121 cells/mm3, and median time on first-line antiretroviral therapy (1SL) was 24 months. At 6 to 9 months on 2NL, 72.6% (intention to treat [ITT]) and 88.3% (on treatment [OT]) had an undetectable viral load (UDVL). At 12 months, 65.8% (ITT) and 90.57% (OT) had UDVL. At >12 to 24 months and at >24 months, 57.5% (ITT) and 91.3% (OT) had UDVL. No statistically significant association was observed between CD4 at 2NL start, sex, genotypic sensitivity score of 2NL, or tenofovir (TDF) use in 1SL and viral suppression. Two patients developed major protease inhibitor mutations while on 2NL. We observed a high degree of viral suppression at 12 months and little loss of viral suppression thereafter.
The Association of Systemic Microvascular Changes with Lung Function and Lung Density: A Cross-Sectional Study

Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV1) (P<0.001) and FEV1/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV1 (P = 0.002) but not FEV1/FVC. Myocardial blood flow (n = 126) was associated with lower FEV1 (P = 0.02), lower FEV1/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.
Cofilin-induced unidirectional cooperative conformational changes in actin filaments revealed by high-speed atomic force microscopy

High-speed atomic force microscopy was employed to observe structural changes in actin filaments induced by cofilin binding. Consistent with previous electron and fluorescence microscopic studies, cofilin formed clusters along actin filaments, where the filaments were 2-nm thicker and the helical pitch was ∼25% shorter, compared to control filaments. Interestingly, the shortened helical pitch was propagated to the neighboring bare zone on the pointed-end side of the cluster, while the pitch on the barbed-end side was similar to the control. Thus, cofilin clusters induce distinctively asymmetric conformational changes in filaments. Consistent with the idea that cofilin favors actin structures with a shorter helical pitch, cofilin clusters grew unidirectionally toward the pointed-end of the filament. Severing was often observed near the boundaries between bare zones and clusters, but not necessarily at the boundaries. DOI: http://dx.doi. org/10.7554/eLife.04806. 001
Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation

In their mammalian hosts, Leishmania are obligate intracellular parasites that mainly reside in macrophages. They are also phagocytosed by dendritic cells (DCs), which play decisive roles in the induction and shaping of T cell-dependent immune responses. Little is known about the role of DCs in the Leishmania life cycle. Here, we examined the ability of mouse bone marrow-derived DCs to serve as hosts for L. amazonensis. Both infective stages of Leishmania (metacyclic promastigotes and amastigotes) could be phagocytosed by DCs, regardless of whether they had previously been experimentally opsonized with either the complement C3 component or specific antibodies. Parasites could survive and even multiply in these cells for at least 72 hours, within parasitophorous vacuoles displaying phagolysosomal characteristics and MHC class II and H-2M molecules. We then studied the degree of maturation reached by infected DCs according to the parasite stage internalised and the type of opsonin used. The cell surface expression of CD24, CD40, CD54, CD80, CD86, OX40L and MHC class II molecules was barely altered following infection with unopsonized promastigotes or amastigotes from nude mice or with C3-coated promastigotes. Even 69 hours post-phagocytosis, a large proportion of infected DCs remained phenotypically immature. In contrast, internalisation of antibody-opsonized promastigotes or amastigotes induced DCs to mature rapidly, as shown by the over-expression of costimulatory, adhesion and MHC class II molecules. Thus, in the absence of specific antibodies (e.g. shortly after infecting naive mammals), infected DCs may remain immature or semi-mature, meaning that they are unable to elicit an efficient anti-Leishmania T cell response. Absence of DC maturation or delayed/incomplete DC maturation could thus be beneficial for the parasites, allowing their establishment and amplification before the onset of immune responses.
Study of the Brainstem, Particularly the Arcuate Nucleus, in Sudden Infant Death Syndrome (SIDS) and Sudden Intrauterine Unexplained Death (SIUD)

Complete examination of the brainstem involves transverse serial 5-&mgr;m sections made throughout the entire brainstem. The number of serial sections varies from 360 in sudden intrauterine unexplained death (SIUD) to 600 in term fetuses to over 1400 sections in sudden infant death syndrome (SIDS) victims. The procedure is not applicable in all histopathological laboratories, owing to the need for additional technical personnel. The simplified procedure allows a remarkable reduction of the number of sections. The brainstem is divided into 3 blocks. The first, cranial block, extends from the border between the medulla oblongata and pons up to the upper pole of the olivary nucleus. The second, intermediate block, corresponding to the submedian area of the inferior olivary nucleus, has as reference point the obex and extends 2 to 3 mm above and below the obex itself. The third, caudal block, includes the lower pole of the inferior olivary nucleus and the lower adjacent area of the medulla oblongata. Examinations of the brainstems from 106 SIDS victims, 30 controls, and 51 stillborns underlined a remarkable variability, particularly of the arcuate nucleus. The simplified examination of the brainstem makes it possible to evaluate the structures, examining 3 specific levels, defined by morphologic reference points.
Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of “univalents” linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.
Storage of comminuted and uncomminuted forest biomass and its effect on fuel quality

White birch was stored in the form of bundles, wood chips, and loose slash for a period of one year to examine the changes in biomass fuel properties. The samples were collected at regular quarterly intervals to measure moisture content, CNS content, ash content, and calorific value. Data loggers were also placed into the stored woody biomass to measure the temperature change inside the piles. After the first quarter of the storage period and continuing into the next three months of storage, the moisture content showed the most significant change. The moisture content of the biomass bundles increased from 29 % to above 80 % (db). The moisture content of the pile of wood chips covered with a tarp decreased from 51% to 26% and showed a continuous decline in moisture content to the end of storage period to an average range of 16.5% (db). However, the moisture content of uncovered wood chip pile was observed to continuously increase throughout the storage period, resulting in more than double in magnitude from 59% to 160% (db). The dry matter loss was higher in wood chip piles (8~27%) than in bundles (~3%). Among the other properties, there was slightly higher loss of calorific value in wood chips (~1.6%) as compared to bundles (~0.7%) at the end of one year.
A Novel Interconnect Camouflaging Technique using Transistor Threshold Voltage

Semiconductor supply chain is increasingly getting exposed to variety of security attacks such as Trojan insertion, cloning, counterfeiting, reverse engineering (RE) and piracy of Intellectual Property (IP) due to involvement of untrusted parties. Camouflaging of gates has been proposed to hide the functionality of gates. However, gate camouflaging is associated with significant area, power and delay overhead. In this paper, we propose camouflaging of interconnects using multiplexers (muxes) to protect the IP. A transistor threshold voltage-defined pass transistor mux is proposed to prevent its reverse engineering since transistor threshold voltage is opaque to the adversary. The proposed mux with more than one input, hides the original connectivity of the net. The camouflaged design operates at nominal voltage and obeys conventional reliability limits. A small fraction of nets can be camouflaged to increase the RE effort extremely high while keeping the overhead low. We propose controllability, observability and random net selection strategy for camouflaging. Simulation results indicate 15-33% area, 25-44% delay and 14-29% power overhead when 5-15% nets are camouflaged using the proposed 2:1 mux. By increasing the mux size to 4:1, 8:1, and 16:1, the RE effort can be further improved with small area, delay, and power penalty.
Thermal and barrier properties of EVOH/EFG nanocomposite films for packaging applications: Effect of the mixing method

Ethylene-vinyl alcohol copolymer (EVOH)/exfoliated graphite (EFG) nanocomposite films were prepared by precoating EFG on the EVOH surface and conducting a successive melt-extrusion process. Their physical properties were strongly dependent on the EFG content and the mixing method, which strongly affected the morphology and surface properties of the nanocomposite films. The hydrophobicity and water resistance property of EVOH increased by incorporating hydrophobic EFG and their effects were more pronounced in the precoating method, which is related to good dispersion of EFG in EVOH and an enhanced crystalline structure. The incorporation of EFG into EVOH by the precoating method more effectively diminished the dependence of the relative humidity on the oxygen transmission rate of pure EVOH and increased the oxygen barrier properties of EVOH at a high relative humidity. The incorporation of EFG into EVOH by the precoating method also induced relatively more enhanced thermal stability. These results suggest the feasibility of the application of moisture-sensitive EVOH resin for food packaging films. POLYM. COMPOS. , 2014. © 2014 Society of Plastics Engineers