Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic gating of the proton pump in cytochrome c oxidase

Cytochrome c oxidase (CcO), the terminal enzyme of the respiratory chain, reduces oxygen to water and uses the released energy to pump protons across a membrane. Here, we use kinetic master equations to explore the energetic and kinetic control of proton pumping in CcO. We construct models consistent with thermodynamic principles, the structure of CcO, experimentally known proton affinities, and equilibrium constants of intermediate reactions. The resulting models are found to capture key properties of CcO, including the midpoint redox potentials of the metal centers and the electron transfer rates. We find that coarse-grained models with two proton sites and one electron site can pump one proton per electron against membrane potentials exceeding 100 mV. The high pumping efficiency of these models requires strong electrostatic couplings between the proton loading (pump) site and the electron site (heme a), and kinetic gating of the internal proton transfer. Gating is achieved by enhancing the rate of proton transfer from the conserved Glu-242 to the pump site on reduction of heme a, consistent with the predictions of the water-gated model of proton pumping. The model also accounts for the phenotype of D-channel mutations associated with loss of pumping but retained turnover. The fundamental mechanism identified here for the efficient conversion of chemical energy into an electrochemical potential should prove relevant also for other molecular machines and novel fuel-cell designs.
Long-range pseudoknot interactions dictate the regulatory response in the tetrahydrofolate riboswitch

Tetrahydrofolate (THF), a biologically active form of the vitamin folate (B9), is an essential cofactor in one-carbon transfer reactions. In bacteria, expression of folate-related genes is controlled by feedback modulation in response to specific binding of THF and related compounds to a riboswitch. Here, we present the X-ray structures of the THF-sensing domain from the Eubacterium siraeum riboswitch in the ligand-bound and unbound states. The structure reveals an “inverted” three-way junctional architecture, most unusual for riboswitches, with the junction located far from the regulatory helix P1 and not directly participating in helix P1 formation. Instead, the three-way junction, stabilized by binding to the ligand, aligns the riboswitch stems for long-range tertiary pseudoknot interactions that contribute to the organization of helix P1 and therefore stipulate the regulatory response of the riboswitch. The pterin moiety of the ligand docks in a semiopen pocket adjacent to the junction, where it forms specific hydrogen bonds with two moderately conserved pyrimidines. The aminobenzoate moiety stacks on a guanine base, whereas the glutamate moiety does not appear to make strong interactions with the RNA. In contrast to other riboswitches, these findings demonstrate that the THF riboswitch uses a limited number of available determinants for ligand recognition. Given that modern antibiotics target folate metabolism, the THF riboswitch structure provides insights on mechanistic aspects of riboswitch function and may help in manipulating THF levels in pathogenic bacteria.
Receptors, signal transduction, and spectrum of action of monocyte chemotactic protein‐1 and related chemokines

Chemokines are a bipartite family of chemotactic proteins that bear the structural hallmark of four cysteine residues, the first two of which are in tandem. The spectrum of action of C‐C chemokines, monocyte chemotactic protein‐1 (MCP‐1), MCP‐2, and MCP‐3, in particular, encompasses, in addition to monocytes, other leukocyte populations. Evidence is presented that MCP‐1, MCP‐2, and MCP‐3 are active on natural killer cells. Available information on receptor usage by MCP‐1 and related chemokines and signal transduction pathways is reviewed. A better understanding of signaling mechanisms will provide a new basis for therapeutic strategies. J. Leukoc. Biol. 57: 788–794; 1995.
Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders.

OBJECTIVE The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID). METHODS Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and "optimal dose" for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD). RESULTS MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects. CONCLUSION The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.
Cervical disc arthroplasty: Pros and cons

Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing.
A Low Phase Noise  $LC$ VCO in 65 nm CMOS Process Using Rectangular Switching Technique

A low phase noise and low power LC voltage-controlled oscillator (VCO) has been designed using a 65-nm CMOS process. The phase noise is minimized by switching the differential core using a rectangular shaped voltage waveform, which is formed by a harmonic tuned LC tank assisted by a gm3 boosting circuit. The gm3 boosting circuit effectively maximizes the slope at the zero crossing point and reduces the transition time in which the switching transistor is operated at the triode region. The rectangular switching technique has improved the phase noise of the oscillator by 10 dB. The 450 mum times 540 mum chip consumes 4.34 mW. The proposed VCO has phase noises of -83.3, -110.7, and -131.8 dBc/Hz at 10 KHz, 100 KHz, and 1 MHz offset frequencies, respectively, from the 1.6-GHz carrier frequency.
Time-frequency diffusion analysis for DOA estimation of tropospheric scatter signal

DOA estimation is a hot topic in tropospheric scatter radar target reconnaissance Over-The-Horizon (OTH). The received signal propagated through troposphere OTH is so weak because of strong loss, the classical MUSIC has been unable to effectively estimate angle. So we adopt Time-Frequency (TF) MUSIC, i.e., replacing the array covariance matrix of the classical MUSIC with Time-Frequency Distribution (TFD) matrix, which is suitable for the low Signal-to-Noise Ratio (SNR) condition. In order to effectively processing signal, the troposcatter signal characteristics should be modeled and analyzed. Firstly, we analyze troposcatter propagation loss, and further deduce the receiver output SNR to provide support for algorithm design. Secondly, considering that time, frequency diffusion in energy caused by troposcatter multipath fading, we derive time-delay and frequency-shift diffusion functions based on scatter transmission function. To be more specific, the diffusion characteristics are studied on the variations of the beam width, target distances etc. Then we deduce the joint time-frequency diffusion function and coefficient from the above two diffusions. Affected by the diffusion, the TFD matrix will be distorted to degrade the algorithm accuracy. To utilize the characteristic, we propose a weighted scattering signal TFD matrix, where the weight matrix is derived from the joint diffusion coefficient, to prominent the scattering signal according to the matched filter theory. Then we can estimate exactly angle for the troposcatter signal using the weighted matrix.
Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

1 We have studied the occurrence, distribution and disposition of lipocortins (annexins) 1, 2 and 5 in mixed peritoneal leucocytes obtained from rats in which glucocorticoid levels were altered by adrenalectomy, administration of the glucocorticoid antagonist, RU486, or by injection of dexamethasone or hydrocortisone, as well as from rats in which the peritoneal cells were elicited by inflammatory stimuli. 2 In cells obtained from untreated rats with an intact adrenal cortex, lipocortins 1, 2 and 5 were readily detectable: the majority of each of the proteins was apparently located intracellularly with much smaller amounts in the membrane. Lipocortin 1 and to a lesser extent lipocortin 5 were also seen in a Ca2+‐dependent association with the external plasma membrane. Following administration of RU486 (2 × 20 mg kg−1) the amounts of lipocortin 1 and 2 in cells were greatly reduced. Conversely, injection of hydrocortisone (1 mg kg−1) or dexamethasone (0.08 mg kg−1) caused an increase in the amount of lipocortin 1 and 2 in peritoneal cells within 30 min. Lipocortin 5 was unchanged by any manipulation of glucocorticoid levels. 3 Lipocortins 1 and 2 were elevated in both intracellular and membrane‐associated fractions of macrophages elicited by intraperitoneal injection in inflammogens. This phenomenon also occurred in adrenalectomized animals. 4 Our data indicate that glucocorticoids control the synthesis of some members of the lipocortin family in rat mixed peritoneal cells but also suggest the existence of a separate system for controlling the generation of this protein. The significance of these observations is considered in relation to the mechanism of glucocorticoid hormone action on eicosanoid production.
Contribution of secondary structure to the heat capacity and enthalpy distribution of the unfolded state in proteins.

We have recently shown that one can construct the enthalpy distribution for protein molecules from experimental knowledge of the temperature dependence of the heat capacity. For many proteins the enthalpy distribution evaluated at the midpoint of the denaturation transition (corresponding to the maximum in the heat capacity vs temperature curve) is broad and biphasic, indicating two different populations of molecules (native and unfolded) with distinctly different enthalpies. At temperatures above the denaturation point, the heat capacity for the unfolded state in many proteins is quite large and using the analysis just mentioned, we obtain a gaussian-like enthalpy distribution that is very broad. A large value of the heat capacity indicates that there are structural changes going on in the unfolded state above the transition temperature. In the present paper we investigate the origin of this large heat capacity by considering the presence of changing amounts of secondary structure (specifically, alpha-helix) in the unfolded state. For this purpose we use the empirical estimates of the Zimm-Bragg sigma and s factors for all of the native amino acids in water as determined by Scheraga and co-workers. Using myoglobin as an example, we calculate probability profiles and distribution functions for the total number of helix states in the specific-sequence molecule. Given the partition function for the specific-sequence molecule, we can then calculate a set of enthalpy moments for the molecule from which we obtain a good estimate of the enthalpy distribution in the unfolded state. This distribution turns out to be quite narrow when compared with the distribution obtained from the raw heat capacity data. We conclude that there must be other major structural changes (backbone and solvent) that are not accounted for by the inclusion of alpha-helix in the unfolded state.
Effects of Treating Exhaustion in Angioplasty Patients on New Coronary Events: Results of the Randomized Exhaustion Intervention Trial (EXIT)

Background: Extreme fatigue is a common complaint in percutaneous coronary intervention (PCI) patients, and is associated with an increased risk for new cardiac events. The objective of the Exhaustion Intervention Trial (EXIT) was to determine whether a behavioral intervention on exhaustion reduces the risk of a new coronary event after PCI. Methods and Results: Seven hundred ten consecutive patients, ages 35 to 68 years, who felt exhausted after PCI were randomized into an intervention group and a usual-care group. The intervention was based on group therapy focusing on stressors leading to exhaustion, and on support for recovery by promoting rest and making rest more efficient. One month after PCI, 50% of the patients felt exhausted. The intervention reduced the odds of remaining exhausted at 18 months by 56% in those without a previous history of coronary artery disease (CAD) (OR = 0.44; 95% CI 0.29–0.66), but had no effect on exhaustion in those with a history of CAD (OR = 0.93; 95% CI 0.56–1.55; p = .78). The intervention did not reduce the risk of a new coronary event within 2 years (RR = 1.14; 95%CI 0.82–1.57). Post-hoc analyses suggest that the effect of the intervention was limited by a positive history of CAD, the presence of a chronic, painful condition (especially rheumatism), and by opposite effects on early and late cardiac events. Conclusion: A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion. It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years. PCI = percutaneous coronary intervention; CAD = coronary artery disease; MQ = Maastricht Questionnaire; MIVE = Maastricht Interview Vital Exhaustion; EXIT = Exhaustion Intervention Trial; CABG = coronary artery bypass graft; MI = myocardial infarction.
Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration

This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.
A study of farmers seed selection methods in the Kpandai district of the northern region of Ghana

Low productivity of agricultural crops is among the factors leading to low income and food insecurity for rural folks in most farming communities in Ghana. One measure in which productivity could be boosted is through the use improved seeds. Among other agricultural inputs, seed is probably the most important input to farmers, thus for seed to be catalyst in agricultural production the source must be regular and the methods of seed selection must be effective. However it should be appreciated that little has been done to understand how informal seed development operates though many interventions have been put in place to cope with farmer’s seed insecurity. This paper accesses farmer’s practices for maintaining seed security in Kpandai district of the Northern region of Ghana which provides a broader picture of the various sources of seeds available to farmers. The discussion explores the possibilities of blending traditional and modern science to ensure regular supply and good quality seed to farmers at all times. Helping poor farmers’ access good quality seed will not only increase their productivity but also sustain their interest in the farming activities.
New perspectives for the study of lucid dreaming: From brain stimulation to philosophical theories of self-consciousness Commentary on "The neurobiology of consciousness: Lucid dreaming wakes up" by J. Allan Hobson

The neural mechanisms underlying lucid dreaming have recently been investigated using brain imaging techniques such as electroencephalography and functional magnetic resonance imaging, which produce insightful but merely correlative results. We propose that research on the neurophysiology of lucid dreaming, for instance concerning the exact relationship between the dorsolateral prefrontal cortex and metacognitive insight into the fact that one is dreaming, should be complemented by methods allowing direct causal interference with neural functioning during sleep. To achieve this aim, several stimulation methods are proposed, i.e. transcranial magnetic stimulation, transcranial direct current stimulation, and galvanic vestibular stimulation. Given the broad range of cognitive and metacognitive processing in dreams, which support a continuous view of lucid and nonlucid dreaming, we further propose that certain aspects of dream lucidity and its neural mechanisms can be investigated in so-called ordinary, nonlucid dreams. This would allow for phenomenologically more comprehensive and practically more efficient experiments in this field of dream research. Such experiments would also provide a solid ground for understanding self-consciousness in lucid and non-lucid dreams, as well as for integrating dream research into more general neurophilosophical theories of consciousness and the self.
Risk of mortality with a bloodstream infection is higher in the less severely ill at admission.

RATIONALE Health care-associated bloodstream infections are common in critically ill patients; however, investigators have had difficulty in quantifying the clinical impact of these infections given the high expected mortality among these patients. OBJECTIVE To estimate the impact of health care-associated bloodstream infections on in-hospital mortality after adjusting for severity of illness at critical care admission. METHOD A cohort of medical and surgical intensive care unit patients. MEASUREMENTS Severity of illness at admission, bloodstream infection, and in-hospital mortality. MAIN RESULTS Among the 2,783 adult patients, 269 developed unit-associated bloodstream infections. After adjusting for severity of illness, patients with a lower initial severity of illness who developed an infection had a greater than twofold higher risk for in-hospital mortality (hazard ratio [HR] = 2.42, 95% confidence interval [CI] 1.70, 3.44) when compared with patients without infection and with a similar initial severity of illness. In contrast, patients with a higher initial severity of illness who subsequently developed an infection did not have an increased risk for in-hospital mortality (HR = 0.96, 95%CI 0.76, 1.23) when compared with patients without infection but with a similar initial severity of illness. CONCLUSIONS These results suggest that these infections in less ill patients have a higher attributable impact on subsequent mortality than in more severely ill patients. Focusing interventions to prevent bloodstream infections in less severely ill patients would be expected to have a greater benefit in terms of mortality reduction.
Compliance with the building byelaws and earthquake safety in urban areas of Bihar: progress, constraints and challenges

ABSTRACT The adoption and enforcement of building codes is considered the most effective tool in safeguarding lives and property against earthquakes. There would appear to be a vital regulatory role for government in the enforcement of building codes, but this is somewhat at odds with the neoliberal agenda of ‘rolling back the state’. This paper explores constraints to the implementation of building codes in the context of changing roles and responsibilities of local authorities in Bihar in India. In-depth interviews were conducted with key stakeholders across major urban centres in north Bihar. Some factors, such as: code complexity; competition between the public and private sectors for qualified personnel; and low public risk perception were found to be less significant in Bihar than has been noted elsewhere, while other factors such as: the cost of earthquake-resistant measures; political interests; corrupt practices; and lack of government capacity were important. Additional factors were also revealed by the research, some of which are exacerbated by the neoliberal climate of urban governance. While the recent 2014 byelaws represent an improvement in the system and a degree of re-regulation, ambiguities create opportunities for failures arising from ‘normalised irresponsibility’.
Implications of Trans-Pacific Partnership for the US Dairy Industry

The Trans-Pacific Partnership (TPP) agreement would reduce or eliminates tariff and nontariff barriers to trade and increase investment among the parties. Dairy exporting countries in the TPP, including the United States, will compete for market share. This study aims to investigate the possible change in dairy trade flows if the TPP agreement is enacted and the implications for the US dairy industry. An empirical trade simulation model is developed focusing on US dairy trade to analyze the potential impacts.
Cases of advanced visual field loss at referral to glaucoma clinics – more men than women?

In many medical conditions ‘late presentation’ of disease is more of a problem for men than women. Risk of sight loss from glaucoma is certainly greater in those detected with advanced disease. We performed a retrospective study to test the hypothesis that men are more likely than women to have advanced visual field loss at referral to glaucoma clinics.