Miracle-dz/UniFAR-FTUs huggingface dataset:
Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a dutch cohort.

RATIONALE Familial clustering of adult idiopathic interstitial pneumonias (IIP) suggests that genetic factors might play an important role in disease development. Mutations in the gene encoding surfactant protein C (SFTPC) have been found in children and families with idiopathic pneumonias, whereas cocarriage of a mutation in ATP-binding cassette subfamily A member 3 (ABCA3) was postulated to have a disease-modifying effect. OBJECTIVES To investigate the contribution of SFTPC mutations to adult familial pulmonary fibrosis (FPF) and the disease-modifying effect of mutations in ABCA3 within their families. METHODS Twenty-two unrelated patients with FPF (10%) were identified within our single-center cohort of 229 patients with IIP. SFTPC was sequenced in 20 patients with FPF and 20 patients with sporadic IIP. In patients with an SFTPC mutation, sequencing of ABCA3 was performed. Discovered variants were typed in more than 100 control subjects and 121 additional patients with sporadic IIP. MEASUREMENTS AND MAIN RESULTS In 5/20 unrelated patients with FPF (25%; confidence interval, 10-49) a mutation in SFTPC was detected: M71V, IVS4+2, and three times I73T. No mutations were detected in the sporadic or control cohort. Patients with SFTPC mutations presented with a histopathological pattern of usual interstitial pneumonia and nodular septa thickening and multiple lung cysts in combination with ground glass or diffuse lung involvement on chest high-resolution computed tomography. Two variants in ABCA3 were found in adult patients with FPF but not in affected children. CONCLUSIONS Mutations in SFTPC are a frequent cause of FPF in adult patients in our cohort. Nonclassifiable radiological patterns with cystic changes and histopathological patterns of usual interstitial pneumonia are characteristics of adult SFTPC mutation carriers.
Triglyceride-to-HDL cholesterol ratio in the dyslipidemic classification of type 2 diabetes.

Although LDL cholesterol is the main target in the treatment of diabetic dyslipidemia, it does not fully account for the cardiovascular risk associated with diabetes, neither alone nor in combination with triglycerides and HDL cholesterol. On the other hand, diabetic dyslipidemia also includes an overall increase in atherogenic particles identifiable, by measuring apolipoprotein B (apoB), and a predominance of small, dense LDL particles (phenotype B). The latter, although associated with increased cardiovascular risk, is not routinely assessed because its measurement is not available to most clinical laboratories. Therefore, easily measurable predictors of LDL size, such as triglycerides or LDL cholesterol/apoB and triglyceride–to–HDL cholesterol ratios, have been proposed, with the latter being suggested as the best surrogate (1,2,3). However, no study has been conducted that compares all of these predictors. The aim of the present study is to evaluate the triglyceride–to–HDL cholesterol ratio, non-HDL cholesterol, and apoB to predict LDL phenotype and to assess them in the risk classification of patients with type 2 diabetes. A total of 107 type 2 diabetic patients (68% male, age 59 ± 10 years [means ± SD], time since diagnosis 8.5 years [range 0–37], HbA1c 7.35% [3.7–16]) were consecutively included in the study. None of the patients were taking drugs or were in situations (not related to diabetes) known to affect lipoprotein metabolism. Total cholesterol and triglycerides were measured by enzymatic methods and HDL cholesterol by a direct method (Roche Diagnostics, Basel, Switzerland). Hypertriglyceridemia was defined by triglycerides >2.25 mmol/l (4, …
Central obesity and breast cancer risk: a systematic review

The specific effect of central rather than general obesity on breast cancer risk is not clear. This review examines the relationship between waist and waist–hip ratio (WHR) and risk of breast cancer in pre‐ and post‐menopausal women using all available cohort and case‐control data. The databases of the Cochrane Library, Medline, Cancer Lit and Embase were searched until October 2002. Relevant cohort and case‐control studies with separate analyses in pre‐ and/or post‐menopausal women were included. Random effects meta‐analyses were carried out, subgrouped by pre‐ or post‐menopausal status and cohort or case‐control design. Sensitivity analyses were also performed. Five cohort studies with 72 1705 person years of observation (453 pre‐menopausal and 2684 post‐menopausal cases), and three case‐control studies comprising 276 pre‐menopausal cases with 758 pre‐menopausal controls and 390 post‐menopausal cases with 1071 post‐menopausal controls were included. Pooled results from cohort studies using the most adjusted data [but without adjustment for weight or body mass index (BMI)] suggest a 39% lower risk of breast cancer in post‐menopausal women with the smallest waist (compared with the largest) and a 24% lower risk in women with the smallest WHR. In pre‐menopausal women, however, pooled results suggest that measurement of waist or WHR have little effect on risk of breast cancer. Adjustment for BMI abolished the relationship between waist or WHR and risk of post‐menopausal breast cancer, but introduced such a relationship amongst pre‐menopausal women. The relationship between a smaller measurement of waist or WHR and lower risk of post‐menopausal breast cancer appears to result from the associated correlation with BMI. Amongst pre‐menopausal women, central (not general) obesity may be specifically associated with an increased risk of breast cancer.
Functional programming and embedded systems

Embedded computer systems seem to be the antithesis of functional language systems. Embedded systems are small, stand-alone, and are often forced to accept inelegant design compromises due to hardware cost. They run continuously and are reactive, that is, their primary goal is to monitor sensors and control effectors, using observed external events to trigger state-changing control actions. Yet this thesis describes how functional abstraction can tame the inelegance of embedded systems. Architectural compromises can be made in device drivers, programmed within the functional language, but a function-level interface is presented to the application programmer. Four modifications are introduced to a test-bed purely-functional language in order to facilitate embedded-systems programming: I/O register access; communicating processes; interrupts; and a real-time incremental garbage collector. Referential transparency is preserved. The conventional model of communicating processes is augmented by the use of type classes and constructor classes to add type security around message-passing. Two case studies of embedded applications are programmed: a marble-sorter and a liftshaft. Both give encouraging results for the adequacy of the approach. Two important areas are identified for future research. (1) It is not clear to what extent lazy evaluation is a help or a hindrance in programming embedded systems. (2) Real-time expression and guarantees of schedulability would extend the attractiveness of functional languages still further.
Surface and Dynamic Structures of Bacteriorhodopsin in a 2D Crystal, a Distorted or Disrupted Lattice, as Revealed by Site‐directed Solid‐state 13C NMR †

The 3D structure of bacteriorhodopsin (bR) obtained by X‐ray diffraction or cryo‐electron microscope studies is not always sufficient for a picture at ambient temperature where dynamic behavior is exhibited. For this reason, a site‐directed solid‐state 13C NMR study of fully hydrated bR from purple membrane (PM), or a distorted or disrupted lattice, is very valuable in order to gain insight into the dynamic picture. This includes the surface structure, at the physiologically important ambient temperature. Almost all of the 13C NMR signals are available from [3‐13C]Ala or [1‐13C]Val‐labeled bR from PM, although the 13C NMR signals from the surface areas, including loops and transmembrane α‐helices near the surface (8.7 Å depth), are suppressed for preparations labeled with [1‐13C]Gly, Ala, Leu, Phe, Tyr, etc. due to a failure of the attempted peak‐narrowing by making use of the interfered frequency of the frequency of fluctuation motions with the frequency of magic angle spinning. In particular, the C‐terminal residues, 226–235, are present as the C‐terminal α‐helix which is held together with the nearby loops to form a surface complex, although the remaining C‐terminal residues undergo isotropic motion even in a 2D crystalline lattice (PM) under physiological conditions. Surprisingly, the 13C NMR signals could be further suppressed even from [3‐13C]Ala‐ or [1‐13C]Val‐bR, due to the acquired fluctuation motions with correlation times in the order of 10−4 to 10−5 s, when the 2D lattice structure is instantaneously distorted or completely disrupted, either in photo‐intermediate, removed retinal or when embedded in the lipid bilayers.
Scaffold Function of Ca2+-Dependent Protein Kinase: Tobacco Ca2+-DEPENDENT PROTEIN KINASE1 Transfers 14-3-3 to the Substrate REPRESSION OF SHOOT GROWTH after Phosphorylation1[C][W]

A Ca2+-dependent protein kinase not only phosphorylates a substrate but also acts as a scaffold that promotes the interaction between a phosphorylation product and its binding protein. A molecular mechanism to ensure signaling specificity is a scaffold. REPRESSION OF SHOOT GROWTH (RSG) is a tobacco (Nicotiana tabacum) transcription factor that is involved in gibberellin feedback regulation. The 14-3-3 proteins negatively regulate RSG by sequestering it in the cytoplasm in response to gibberellins. The N. tabacum Ca2+-dependent protein kinase NtCDPK1 was identified as an RSG kinase that promotes 14-3-3 binding of RSG by phosphorylation of RSG. CDPKs are unique sensor responders of Ca2+ that are only found in plants and some protozoans. Here, we report a scaffolding function of CDPK. 14-3-3 proteins bound to NtCDPK1 by a new mode. Autophosphorylation of NtCDPK1 was necessary for the formation of the binding between NtCDPK1 and 14-3-3 but not for its maintenance. NtCDPK1 formed a heterotrimer with RSG and 14-3-3. Furthermore, we found that NtCDPK1 transfers 14-3-3 to RSG after phosphorylation of RSG and that RSG dissociates from NtCDPK1 as a complex with 14-3-3. These results suggest that NtCDPK1 is an interesting scaffolding kinase that increases the specificity and efficiency of signaling by coupling catalysis with scaffolding on the same protein.
Improved decoding of binary Golay code

The triple-error-correcting binary Golay code has been used in DNA and communication systems. Recently, an algebraic decoding of the Golay code has been proposed by an unusual general error locator polynomials (GELP). This paper utilizes the interpolation method to obtain a new unusual GELP. Simulation results show that the Golay decoder using the presented unusual GELP significantly reduces the area and latency compared to the existing Golay decoders.
Autism and the gastrointestinal tract

development of rational treatments that can be based on biological control mechanisms of dormancy or clearance. Whether specific immune, antiangiogenic, or chemoradiotherapeutic strategies are adopted, the study of systemic micrometastatic disease in esophageal cancer will be critical for predicting and assessing clinical responsiveness, and is likely to provide valuable insights for the management of other solid tumors.
Decreased Pathology and Prolonged Survival of Human DC-SIGN Transgenic Mice during Mycobacterial Infection1

Dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN: CD209) is a C-type lectin that binds ICAM-2,3 and various pathogens such as HIV, helicobacter, and mycobacteria. It has been suggested that Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, interacts with DC-SIGN to evade the immune system. To directly analyze the role of human DC-SIGN during mycobacterial infection, we generated conventional transgenic (tg) mice (termed “hSIGN”) using CD209 cDNA under the control of the murine CD11c promoter. Upon mycobacterial infection, DCs from hSIGN mice produced significantly less IL-12p40 and no significant differences were be observed in the secretion levels of IL-10 relative to control DCs. After high dose aerosol infection with the strain M. tuberculosis H37Rv, hSIGN mice showed massive accumulation of DC-SIGN+ cells in infected lungs, reduced tissue damage and prolonged survival. Based on our in vivo data, we propose that instead of favoring the immune evasion of mycobacteria, human DC-SIGN may have evolved as a pathogen receptor promoting protection by limiting tuberculosis-induced pathology.
Wave-variable framework for networked robotic systems with time delays and packet losses

ABSTRACT This paper investigates the problem of networked control system for nonlinear robotic manipulators under time delays and packet loss by using passivity technique. With the utilisation of wave variables and a passive remote controller, the networked robotic system is demonstrated to be stable with guaranteed position regulation. For the input/output signals of robotic systems, a discretisation block is exploited to convert continuous-time signals to discrete-time signals, and vice versa. Subsequently, we propose a packet management, called wave-variable modulation, to cope with the proposed networked robotic system under time delays and packet losses. Numerical examples and experimental results are presented to demonstrate the performance of the proposed wave-variable-based networked robotic systems.
Mechanical properties and structure‐function relationships of human chondrocyte‐seeded cartilage constructs after in vitro culture

Autologous Chondrocyte Implantation (ACI) is a widely recognized method for the repair of focal cartilage defects. Despite the accepted use, problems with this technique still exist, including graft hypertrophy, damage to surrounding tissue by sutures, uneven cell distribution, and delamination. Modified ACI techniques overcome these challenges by seeding autologous chondrocytes onto a 3D scaffold and securing the graft into the defect. Many studies on these tissue engineered grafts have identified the compressive properties, but few have examined frictional and shear properties as suggested by FDA guidance. This study is the first to perform three mechanical tests (compressive, frictional, and shear) on human tissue engineered cartilage. The objective was to understand the complex mechanical behavior, function, and changes that occur with time in these constructs grown in vitro using compression, friction, and shear tests. Safranin‐O histology and a DMMB assay both revealed increased sulfated glycosaminoglycan (sGAG) content in the scaffolds with increased maturity. Similarly, immunohistochemistry revealed increased lubricin localization on the construct surface. Confined compression and friction tests both revealed improved properties with increased construct maturity. Compressive properties correlated with the sGAG content, while improved friction coefficients were attributed to increased lubricin localization on the construct surfaces. In contrast, shear properties did not improve with increased culture time. This study suggests the various mechanical and biological properties of tissue engineered cartilage improve at different rates, indicating thorough mechanical evaluation of tissue engineered cartilage is critical to understanding the performance of repaired cartilage. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2298–2306, 2017.
A Wideband Highly Integrated and Widely Tunable Transceiver for In-Band Full-Duplex Communication

A fully integrated wideband active duplexing transceiver with baseband noise-cancelling duplexing LNAs is presented. The circuit allows in-band full duplex operation with concurrent reception and transmission in the same band or closely-spaced channels. A passive mixer-first architecture is applied here, sharing a single passive mixer to perform simultaneous up-conversion and down-conversion. The bi-directional transparency of the passive mixer allows the duplexing function to be implemented at baseband instead of RF front end. Under the same condition as required for noise cancellation, the baseband duplexing LNAs buffer the transmitter input signals to the mixer while canceling those signals in receive path. Measurements from the transceiver implemented in 65 nm CMOS show a frequency tuning range of 0.1-1.5 GHz with 20 dB, NF as low as 5.5 dB and transmitted power up to -7.1 dBm. A 30 dB linear isolation between receive and transmit is generally maintained across both LO frequency and in-band transmit/receive frequency separation. Significant suppression of transmit-induced noise and nonlinear intermodulation between received and transmitted signals are also achieved.
A Review on Compliant Joint Mechanisms for Lower Limb Exoskeletons

Lower limb exoskeletons are experiencing a rapid development that may suggest a prompt introduction to the market. These devices have an inherent close interaction with the human body; therefore, it is necessary to ensure user’s safety and comfort. The first exoskeletal designs used to represent the human joints as simple revolute joints. This approximation introduces an axial misalignment issue, which generates uncontrollable internal forces. A mathematical description of the said misalignments is provided to better understand the concept and its consequences. This review will only focus on mechanisms aiming to comply with its user.
Comment on: Gorboulev et al. Na+-D-glucose Cotransporter SGLT1 Is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion. Diabetes 2012;61:187–196

The elegant paper from Koepsell and colleagues (1) demonstrates the apical GLUT2 mechanism, but appears at first sight to question its significance. However, when set in a physiological context, the results are those expected from the three roles of SGLT1 and the differences between fed rat and starved mouse. SGLT1 acts as 1 ) a transporter and 2 ) a powerful scavenger. In 2000, my laboratory proposed that SGLT1 also has 3 ) a pivotal regulatory role, controlling the rapid insertion and activation of GLUT2 at the enterocyte apical membrane so that absorptive capacity matches glucose load. …
Abundance of pathogenic bacteria and viral indicators in chlorinated effluents produced by four wastewater treatment plants in the Gauteng Province, South Africa

The failure of South African wastewater treatment plants to produce effluents of a high microbiological quality is a matter of great concern in terms of the pollution of water resources. This study aimed at assessing the effectiveness of 4 wastewater treatment plants in the Gauteng Province, namely the Zeekoegat, Baviaanspoort, Rayton and Refilwe Water Care Works (WCW), in the removal of pathogenic bacteria and viral indicators. Also taken into consideration were free chlorine concentrations and turbidity levels, which were measured using standard methods. Conventional methods and/or polymerase chain reaction (PCR) techniques were used to detect and identify pathogenic bacteria and coliphages. The turbidity ranged from 2.39 to 62.40 NTU and the concentrations of free chlorine ranged from 0.03 to1.60 mg∙l-1 for all plants. Despite high free chlorine residual concentrations in treated effluents, the survival and occurrence of Escherichia coli , Salmonella typhimurium and Vibrio cholerae were significantly higher at Baviaanspoort (100%, 88.2% and 35.3%), Refilwe (87.5%, 59.4% and 21.9%) and Rayton (75%, 38.2% and 9.4%) compared to Zeekoegat, which only showed the survival of E. coli, at a much lower occurrence rate of 8.8%. Somatic and F-RNA coliphages were removed at 15.57 % and 13.96% for Baviaanspoort, 11.62% and 22.42% for Refilwe, 25% and 32.10% for Rayton, and 40.41% and 52.57% for Zeekoegat WCW. Significant correlations were found between pathogenic bacteria and coliphages at all plants (r = 0.765 for Baviaanspoort, r = 0.904 for Zeekoegat, r = 0.680 for Refilwe, r = 0.796 or the Rayton WCW, p < 0.01). A combination of sedimentation, rapid sand filtra tion and chlorination processes was found to be a major prerequisite for the reduction of turbidity levels and viral indicators and the successful removal of pathogenic bacteria in the Zeekoegat WCW. This study therefore suggests an upgrading of the wastwater treatment plants by including processes such as rapid sand filtration and UV disinfection, which have proved to be effective in the removal and inactivation of pathogenic bacteria and viruses.
Circannual and circadian rhythms in the concentration of corticosterone in the plasma of the edible frog (Rana esculenta L.).

For a period of 21 months between May 1974 and September 1976, circadian variations in the plasma concentration of corticosterone were studied by competitive protein-binding techniques in mature male and female edible frogs living in their natural environment. Blood samples were taken from 8 to 12 frogs six times daily and conventional and cosinor methods were used for statistical analysis. Circadian rhythms were not detected during February and March (time of hibernation). Circannual rhythms were detected in three parameters of the circadian rhythm. The mean concentration of corticosterone over a 24 h period (24 h mean) reached a peak on 1 May (between 15 April and 15 May; 95% limits of confidence); the annual mean value of the 24 h means was 1.97 +/- 0.25 (S.E.M.) microgram/100 ml, with an amplitude of 0.66 microgram/100 ml (0.53--0.79 microgram/100 ml; 95% limits of confidence). Circadian variations in the concentration of corticosterone were largest in May (peak of reproductive activity). The times at which the peak concentration of corticosterone occurred showed circannual variations: peak values were detected around 24.00 h in May, 19.00 h in July and 08.00 h in November. Both circadian and circannual variations have therefore been demonstrated in an endocrine function of an amphibian in its natural habitat.
Emerging therapies for heart failure

Although multiple advancements have been made in the treatment of heart failure (HF), mortality rates remain alarmingly high. The accepted arsenal of therapeutics includes a diuretic, digitalis, a β-blocking agent and an inhibitor of the renin-angiotensin-aldosterone system. Despite the employment of a vast array of agents, nearly 300,000 patients in the US die annually with HF as a primary or contributory cause of death. Additional molecular targets are being evaluated in preclinical and clinical settings including vasopeptidase inhibitors, endothelin-1 receptor antagonists, arginine vasopressin antagonists, selective aldosterone blockers, TNF-α blockers and matrix metalloproteinase inhibitors. Although these approaches hold promise as viable therapeutics, a thorough evaluation of clinical benefit from these agents requires additional trials. Future disease-modifying approaches will also undoubtedly include cell transplantation and gene therapy. It is likely that notable advances in HF treatment will come from agents that attenuate myocardial remodelling. Indeed, maintenance or improvement of cardiac structure can attenuate HF development and improve mortality.