Miracle-dz/UniFAR-FTUs huggingface dataset:
Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral

Iron is concentrated in ferritin, a spherical protein with a capacious cavity for ferric nanominerals of <4,500 Fe atoms. Global ferritin structure is very stable, resisting 6 M urea and heat (85°C) at neutral pH. Eight pores, each formed by six helices from 3 of the 24 polypeptide subunits, restrict mineral access to reductant, protons, or chelators. Protein-directed transport of Fe and aqueous Fe3+ chemistry (solubility ≈10−18 M) drive mineralization. Ferritin pores are “gated” based on protein crystals and Fe chelation rates of wild-type (WT) and engineered proteins. Pore structure and gate residues, which are highly conserved, thus should be sensitive to environmental changes such as low concentrations of chaotropes. We now demonstrate that urea or guanidine (1–10 mM), far below concentrations for global unfolding, induced multiphasic rate increases in Fe2+-bipyridyl formation similar to conservative substitutions of pore residues. Urea (1 M) or the nonconservative Leu/Pro substitution that fully unfolded pores without urea both induced monophasic rate increases in Fe2+ chelation rates, indicating unrestricted access between mineral and reductant/chelator. The observation of low-melting ferritin subdomains by CD spectroscopy (melting midpoint 53°C), accounting for 10% of ferritin α-helices, is unprecedented. The low-melting ferritin subdomains are pores, based on percentage helix and destabilization by either very dilute urea solutions (1 mM) or Leu/Pro substitution, which both increased Fe2+ chelation. Biological molecules may have evolved to control gating of ferritin pores in response to cell iron need and, if mimicked by designer drugs, could impact chelation therapies in iron-overload diseases.
Frame synchronization based on multiple frame observations

We consider frame synchronization for fixed frame length communication system with periodically embedded sync words. In the past few decades, numerous researchers have made significant contributions in various aspects. However, it is almost surprising that a scrutinization over the literature reveals to us an important common assumption: frame synchronization decision-making through single-frame observation. Intuition tells us that an enlarged multiple-frame observation set bears the potential to reduce sync word identification ambiguities and also to combat multi-path fading through ¿frame diversity¿. The objective of this work is thus to characterize the performance improvement of using multiple-frame decision rules rather than the single-frame decision rules considered in the previous work. We select the work of Lui and Tan as our standing point, and have conducted a comparative study in a very comprehensive manner. In particular, we shall show that the benefits of multipleframe based decision rules can be substantial. For example, in many cases, the performance of the correlation rule based on double-frame observation is superior to that of the optimum maximum likelihood rule with single-frame observation. While further enlarging the observation period beyond double frames was found to yield diminishing returns.
Postures for Precision: An Ecological Approach to Marksmanship and the Issue of Warfighter Load.

Survivability is directly tied to ones perception-action capabilities, and compromised situational awareness may have consequences for prospective control in critical situations. Firefighters and soldiers are encumbered by equipment that may compromise action-perception coupling, as temporal constraints during critical situations increase the inertial and interactive forces generated during movement. Insofar as perception-action coupling may be affected by these forces; the impacts of equipment on awareness and visuo-motor performance in critical situations is necessary for providing optimal protection to the actor-perceiver. This study examined the constraints of two soldier loads on perception-action coupling during a precision marksmanship task nested in larger event dynamics requiring information pick-up for overall task performance. Participants were required to pick up visual information during a postural transition to upright stance and respond appropriately to that information during a precision marksmanship task. Increased load weights extended time to discriminate target sequences, demonstrating degradation of dynamic visual acuity under load. Increased peak head velocities observed suggest an inability to dissipate energy across the kinetic chain under the combined constraints of load, movement, and visual performance. Marksmanship performance also decreased, with reductions in accuracy and increased firing latency under load. Evaluation of the segmental dynamics underlying marksmanship shows that load ‘pushes’ segments from optimal coupling relations and increases within-trial variability (fixed-point drift and increased variability). Findings
Evaluation of Immediate Discharge Documents — Room for Improvement?

Background: The Immediate Discharge Document is a tool used to communicate patient discharge information between hospitals and general practitioners. The standard of information provided may be variable, and sometimes delayed in arriving at the GP practice. Typed communication from the hospital can also be slow. This can result in difficulty managing patients in the community following their discharge. Our aim was to assess the quantity of information provided on Immediate Discharge Documents, and to assess the time scale taken for GPs to receive written communications from hospitals regarding patient discharges. An audit was initiated using a tool devised from Scottish Intercollegiate Guidelines Network Publication no 5 and involving four general practices within City of Perth, Scotland. Data was collected over a 28-day period in June/July 2001, by examining Immediate Discharge Documents relevant to each practice population received during this period, and by noting the time of arrival of a final typed summary. Data was analysed by Tayside Audit Resource for Primary Care. A total of 244 Documents were audited. Most significant results include basic administrative detail lacking in up to 30%. Of total documents, 13% failed to record a main condition or diagnosis; 93% recorded drug information, but only in 28% were follow up plans clear; 60% were received within five days of discharge, whilst final typed summaries were received from the hospitals within four weeks only in 51%. Conclusion: These results show there to be room for improvement with regard communication of patient discharge information, in regard to both the content of information provided and the time it takes to arrive. We require to raise awareness of this problem amongst hospital colleagues involving clinical governance and audit staff, with the objective to improve the quality and timescale of information transfer. Where this piece fits It is known that effective information transfer between health professionals is vital to optimise patient care. This work gives further impetus to improve the current standard of communication, and confirms a significant time delay that it takes information to reach GPs from the hospital setting.
The Phase Difference Between Neural Drives to Antagonist Muscles in Essential Tremor Is Associated with the Relative Strength of Supraspinal and Afferent Input

The pathophysiology of essential tremor (ET), the most common movement disorder, is not fully understood. We investigated which factors determine the variability in the phase difference between neural drives to antagonist muscles, a long-standing observation yet unexplained. We used a computational model to simulate the effects of different levels of voluntary and tremulous synaptic input to antagonistic motoneuron pools on the tremor. We compared these simulations to data from 11 human ET patients. In both analyses, the neural drive to muscle was represented as the pooled spike trains of several motor units, which provides an accurate representation of the common synaptic input to motoneurons. The simulations showed that, for each voluntary input level, the phase difference between neural drives to antagonist muscles is determined by the relative strength of the supraspinal tremor input to the motoneuron pools. In addition, when the supraspinal tremor input to one muscle was weak or absent, Ia afferents provided significant common tremor input due to passive stretch. The simulations predicted that without a voluntary drive (rest tremor) the neural drives would be more likely in phase, while a concurrent voluntary input (postural tremor) would lead more frequently to an out-of-phase pattern. The experimental results matched these predictions, showing a significant change in phase difference between postural and rest tremor. They also indicated that the common tremor input is always shared by the antagonistic motoneuron pools, in agreement with the simulations. Our results highlight that the interplay between supraspinal input and spinal afferents is relevant for tremor generation.
Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group.

PURPOSE In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. METHODS To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. RESULTS Thirty-seven percent of patients were younger than 365 days, and 64% were > or = 365 days old (4-year event-free survival [EFS] rate +/- SE: 83% +/- 1% [n = 1,339] and 45% +/- 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were > or = 460 days old (4-year EFS rate +/- SE: 82% +/- 1% [n = 1,589] and 42% +/- 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% +/- 3%; n = 135) fell into a lower risk group. CONCLUSION The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.
Absence of leukocytosis in bacteraemic pneumococcal pneumonia.

BACKGROUND Evaluation of patients with respiratory symptoms in primary care medicine is often based on peripheral WBC count that dictates the extent of diagnostic investigation. A normal WBC count may result in a limited investigation, often omitting chest radiography. AIMS To determine the extent to which patients hospitalised with bacteraemic pneumococcal pneumonia have no leukocytosis at presentation. METHODS A retrospective analysis was performed of patients with bacteraemic community-acquired pneumococcal pneumonia from 2000 to 2007 in a community care academic medical centre. Records were reviewed for symptoms, signs, and laboratory data including pneumococcal serotypes, chest radiographs on admission, and outcome. RESULTS 21% of the patients presented with a normal WBC count (16.7% of the children and 25.6% of the adults). Among this population with a normal WBC count at presentation, 90% of the adults and 70% of the children developed leukocytosis within a few days after admission. CONCLUSIONS In this study, in as many as one-fifth of all the patients with bacteraemic pneumococcal pneumonia, there was no leukocytosis at presentation. We therefore suggest that every patient with clinically suspected pneumonia should undergo chest radiography even if the WBC count is normal.
High risk of symptomatic cardiac events in childhood cancer survivors.

PURPOSE To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs). PATIENTS AND METHODS We determined CEs grade 3 or higher: congestive heart failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models. RESULTS Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI, 3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%) compared with other treatments. In the proportional hazards analyses, anthracycline (dose), cardiac irradiation (dose), combination of these treatments, and congenital heart disease were significantly associated with developing a CE. We demonstrated an exponential relationship between the cumulative anthracycline dose, cardiac irradiation dose, and risk of CE. CONCLUSION CCSs have a high risk of developing symptomatic CEs at an early age. The most common CE was CHF. Survivors treated with both anthracyclines and radiotherapy have the highest risk; after 30 years, one in eight will develop severe heart disease. The use of potentially cardiotoxic treatments should be reconsidered for high-risk groups, and frequent follow-up for high-risk survivors is needed.
Outcome and management of patients with large rectoanal intussusception

OBJECTIVES:Rectoanal intussusception is the funnel-shaped infolding of the rectum, which occurs during evacuation. The aims of this study were to evaluate the risk of full thickness rectal prolapse during follow-up of patients with large rectoanal intussusception, and whether therapy improved functional outcome.METHODS:Between September 1988 and July 1997, patients diagnosed with a large rectoanal intussusception by cinedefecography (intussusception ≥ 10 mm, extending into the anal canal) were retrospectively evaluated. Patients with full thickness rectal prolapse on physical examination or cinedefecography were excluded, as were patients with colonic inertia or a history of surgery for rectal prolapse. The patients were divided into three groups according to the treatment received: group I, conservative dietary therapy; group II, biofeedback; and group III, surgery. Outcomes were obtained by postal questionnaires or telephone interviews. Parameters included age, gender, past medical and surgical history, change of bowel habits, fecal incontinence score, and development of full thickness rectal prolapse.RESULTS:Of the 63 patients, 18 were excluded (seven patients had confirmed full thickness rectal prolapse, four had previous surgery for rectal prolapse, three had colonic inertia, and four died). Follow-up data were obtained in 36 (80%) of the remaining 45 patients. The mean follow-up of this group was 45 months (range, 12–118 months). There were 34 women and two men, with a mean age of 72.4 yr (range, 37–91 yr). The mean size of the intussusception was 2.2 cm (range, 1.0–5.0 cm). The patients were classified as follows: group I, 13 patients (36.1%); group II, 13 patients (36.1%); and group III, 10 patients (27.8%). Subjectively, symptoms improved in five (38.5%), four (30.8%), and six (60.0%) patients in the three groups (p > 0.05). Among the patients with constipation, the decrease in numbers of assisted bowel movements per week (time of diagnosis to present) was significantly greater in group II compared to group I (8.1 ± 2.8 vs 0.8 ± 0.5, respectively, p = 0.004). Among the patients with incontinence, incontinence scores improved more in group II as compared to either group I or group III (time of diagnosis to present, 3.7 ± 4.2 to 1.1 ± 5.4 vs 1.4 ± 2.2, respectively, p > 0.05). Six patients (two in group I, three in group II, and one in group III) had the sensation of rectal prolapse on evacuation; however, only one patient in group I developed full thickness rectal prolapse.CONCLUSIONS:This study demonstrated that the risk of full thickness rectal prolapse developing in patients medically treated for large intussusception is very small (1/26, 3.8%). Moreover, biofeedback is beneficial to improve the symptoms of both constipation and incontinence in these patients. Therefore, biofeedback should be considered as the initial therapy of choice for large rectoanal intussusception.
Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse.

The purpose of the present study was to examine the role of mitochondria in the aging process by determining whether the activities of various electron transport chain oxidoreductases are deleteriously affected during aging and whether the hypothesized age-related alterations in different tissues follow a common pattern. Activities of respiratory complexes I, II, III, and IV were measured in mitochondria isolated from brain, heart, skeletal muscle, liver, and kidney of young (3.5 months), adult (12-14 months), and old (28-30 months) C57BL/6 mice. Activities of some individual complexes were decreased in old animals, but no common pattern can be discerned among various tissues. In general, activities of the complexes were more adversely affected in tissues such as brain, heart, and skeletal muscle, whose parenchyma is composed of postmitotic cells, than those in the liver and kidney, which are composed of slowly dividing cells. The main feature of age-related potentially dysfunctional alterations in tissues was the development of a shift in activity ratios among different complexes, such that it would tend to hinder the ability of mitochondria to effectively transfer electrons down the respiratory chain and thus adversely affect oxidative phosphorylation and/or autooxidizability of the respiratory components.
Comparative study of neutrophil activation by chemiluminescence and flow cytometry

Neutrophil activation by phorbol 12-myristate 13-acetate (PMA) and zymosan was assessed by luminol-dependent chemiluminescence (CL) in a novel microtiter plate format and by flow cytometry (FC) based on the oxidation of dihydrorhodamine 123. The results of this comparison demonstrated striking differences in kinetic parameters between these two techniques for neutrophil activation by PMA and zymosan. PMA activation, as determined by FC, was found to be an all-or-none phenomenon in that below a critical concentration of PMA, few cells were positive. Above this concentration, almost all cells were positive; however, the fluorescence intensity of positive cells increased with an increasing PMA concentration until a plateau (maximal) level was reached. In contrast, increasing zymosan concentrations resulted in proportionate increases in the percentage of positive cells until close to 100% of cells were positive. However, the fluorescence intensity of positive cells remained about the same. CL activity increased proportionately with either PMA or zymosan concentration until a maximal level was achieved. The concentration of PMA required for half-maximal activity was about 10-fold higher for FC than for CL, whereas the analogous concentration of zymosan was about 30-fold higher for CL than for FC. In addition, opsonization had only a small negative effect on the ability of zymosan to activate neutrophils, as determined by FC, whereas it had a very large enhancing effect when determined by CL. The differences in kinetic parameters of activation suggest differential sensitivity to particulate (zymosan) versus soluble (PMA) stimulants for FC and CL.
A Novel Field Scaling Method in Electromagnetic Railguns

To overcome the shortcoming of existing field scaling method in electromagnetic railgun, a novel field scaling method with different materials in different scales was proposed. The scaling method was derived based on the governing equations of physical field and projectile dynamics using similarity theory. The results show that field scaling and projectile velocity matching can be achieved simultaneously under the condition of linearly scaling the railgun geometry by using two different materials of lower electrical conductivity in full-scale and higher electrical conductivity in subscale. And the magnetic permeability, mass density, and volumetric specific heat capacity in two kinds of materials should be approximately equal. Aiming at the practical considerations of the negative correlation between mechanical properties and electrical conductivities in existing metals, the scaling method proved that materials of good mechanical properties but lower electrical conductivities can be used in full-scale large-caliber railguns.
Electrophysiology and ocular blood flow in a family with dominant optic nerve atrophy and a mutation in the OPA1 gene

Objective: To characterize the clinical phenotype, with emphasis on electrophysiology and blood flow measurements, of a family with dominant optic nerve atrophy and an identified mutation in the OPA1 gene. Methods: Seven family members were examined. Ophthalmological evaluation included testing of visual acuity, ophthalmolscopy, kinetic perimetry, color vision testing, full-field electroretinography (ERG), multifocal electroretinography (MERG), and multifocal visual evoked potential (MVEP). Retrobulbar arterial blood flow and retinal capillary perfusion was measured in three patients using scanning laser Doppler flowmetry (SLDF) and color Doppler imaging techniques. PCR-SSCP and DNA sequencing determined the presence of a mutation in exon 18 of the OPA1 gene. Results: The clinical characteristics varied considerably in the family. The ERG and the MERG demonstrated normal retinal function, while the MVEP was abnormal in all examined patients. Retinal and optic nerve head capillary perfusion was significantly decreased in the three patients examined with SLDF. Retrobulbar blood flow velocities were significantly decreased in the central retinal and ophthalmic arteries. In all seven examined subjects, a microdeletion (1756–1767del(12 bp)) in the OPA1 gene was identified. Conclusion: Patients with a mutation in the OPA1 gene have a very variable phenotype. MVEP and blood flow measurements are two new objective methods for an easier detection of this specific genetic optic nerve atrophy.