Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemin is kinetically trapped in cytochrome b(5) from rat outer mitochondrial membrane.

Cytochrome b(5) from the outer mitochondrial membrane of rat liver (OM cyt b(5)) is substantially more stable to thermal and chemical denaturation than cytochrome b(5) from the endoplasmic reticulum of bovine liver (microsomal, or Mc cyt b(5)). In contrast, the corresponding apoproteins have similar stability, suggesting stronger interactions between hemin and the polypeptide in OM cyt b(5). Whereas complete transfer of hemin from bovine Mc cyt b(5) to apomyoglobin at pH 5.2 takes less than 1 h, hemin transfer from OM cyt b(5) is unmeasurably slow. Coupled with the previously reported 1:1 ratio of hemin orientational isomers in OM cyt b(5), this finding suggests that the cofactor is kinetically trapped under physiologically relevant conditions. This conclusion is confirmed by (1)H NMR studies which show that the hemin isomeric ratio changes when the protein is incubated for several hours at 68 degrees C. Interestingly, the orientational isomer favored in OM cyt b(5) is the form less favored in all other known cytochromes b(5).
Effect of suspended uncontaminated sediment on persistent organic pollutant release

The transport and fate of persistent organic pollutants (POPs) during resuspension events were investigated using a batch mixing technique. This technique allowed for the determination of sorption and desorption kinetics under more realistic mixing conditions than those used in previous investigations. It was demonstrated that sorption follows second‐order kinetics that are dependent on both POP concentration and the total suspended solids (TSS) of the system. Desorption shows a similar dependence. To further characterize pollutant release, the impact on maximum POP release of suspending uncontaminated sediment concomitantly with contaminated sediment was investigated, as this more accurately models real‐world resuspension events. It was found that even relatively low ratios of uncontaminated to contaminated sediment (1:2) yield a maximum POP release nearly 10 times lower than for systems containing only contaminated sediment. Increasing the ratio of uncontaminated sediment further reduced maximum POP release. These results highlight an important limitation of laboratory desorption experiments and current risk‐assessment models related to dredging operations; under typical field conditions, the impact of dredging on pollutant transport and fate may be greatly overpredicted. Environ Toxicol Chem 2014;33:375–381. © 2013 SETAC
Pharmacological Treatment of a Diffuse Arteriovenous Malformation of the Upper Extremity in a Child

A young girl with an arteriovenous malformation involving the right upper extremity developed rapidly progressive bony destruction that did not respond to embolization. Treatment with marimastat, starting at 3 years of age, resulted in rapid resolution of pain and gradual healing of bony destruction, associated with regression of the intraosseous arteriovenous shunts. New arteriovenous shunts with bony destruction developed over the years and responded to an increase in the dose of marimastat. Interruption of therapy resulted in recurrence of pain and formation of new lesions. The patient has been treated in this way for 12 years with no adverse effects from the drug.
Equilibrium Selection in Stochastic Games

In this paper a selection theory for stochastic games is developed. The theory itself is based on the ideas of Harsanyi and Selten to select equilibria for games in standard form. We introduce several possible definitions for the stochastic tracing procedure, an extension of the linear tracing procedure to the class of stochastic games. We analyze the properties of these alternative definitions. We show that exactly one of the proposed extensions is consistent with the formulation of Harsanyi–Selten for games in standard form and captures stationarity.
Actigraphic Predictors of Depressed Mood in a Cohort of Non-Psychiatric Adults

Objective: Depressed mood is one of the essential features for the diagnosis of major depression. Evidence from the three-site Epidemiologic Catchment Area study (EcA, Baltimore, Durham and Los Angeles) suggests a prevalence of 4.4% of depressive symptoms in the community. In this study, we examined whether depressed mood, as coded in the Alzheimer's Disease Assessment Scale, would be correlated with actigraphic-derived daytime activity and sleep/wake parameters in a non-psychiatric sample. Method: Consenting volunteers were monitored at home for 5 days with a wrist actigraph. On the last day of the recording, they were given a neuropsychological battery including the Alzheimer's Disease Assessment Scale. Results: Daytime activity level was the best predictor of depressed mood as indicated by a logistic regression analysis. The regression model further suggested that sleep onset latency, total time asleep, and time in bed were also significant predictors of depressed mood. Conclusion: This investigation demonstrates that daytime activity level could be used as an index of depressed mood even in a non-psychiatric sample. Further, the results support the notion that depression should be considered more as a continuum rather than as a set of rigid categories.
Adjuvant ovarian suppression in premenopausal breast cancer.

BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain. METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.).
Comparing Sequential and “ Bag of Sections ” Techniques for Musical Genre Classification

A lot of genre classification work to date has gone into exploring features that demarcate genre either at the lowest (sample) level or the highest level (overall acoustic characteristics of the song). Features evaluated at the sample level are more concerned with sonic qualities like timbre and pitch, whereas higher-level features tend to focus on key, mode, tempo, and other descriptive features of the whole song. This paper focuses instead on the space between these two strata in order to evaluate the extent to which structural-level features of music (e.g. chorus or verse level) delimit particular musical genres. The challenge with this level is that one of the most important attributes of musical composition structures is their ordering, and their various repetitions throughout a particular song. As such, this paper compares different models that variously do or do not take sequencing into account in order to quantify the importance of song structure in determining genre.
The effects of potassium, ammonium, calcium, strontium and magnesium on the electrogram and myogram of mammalian heart muscle.

The effects of five cations on the electrogram and myogram of mammalian heart muscle were studied, using the papillary muscle preparation. Increasing potassium concentration produced an inversion of the T deflection, widening of the R deflection and diminution of systolic force. Removal of potassium resulted in a repetitive response to each electrical stimulus. Ammonium ion increased contractile force, and widened the R deflection and the R-T interval. Increasing the concentration of calcium increased the force of contraction and inverted the T deflection. Decreasing the concentration of calcium decreased the force of contraction without affecting the electrogram until, at a calcium level at which no contractile force could be recorded, the R-T interval decreased, and the R-T segment became elevated. Strontium added to a solution containing the usual amount of calcium had an effect indistinguishable from that produced by adding an equimolar amount of calcium. However, when strontium was added to a solution low in calcium, it produced widening of the R-T interval and prolongation of systole. These effects were abolished by adding calcium. Magnesium had no demonstrable effect on either myogram or electrogram.
Continuously Variable Bandwidth Sharp FIR Filters with Low Complexity

In software defined radio (SDR), sharp filters of different bandwidth are required to fine tune the desired channel. This requires different computational resources and large number of filter coefficients. This paper proposes a continuously variable bandwidth sharp finite impulse response (FIR) filter with low distortion and low complexity. For this, a fixed length FIR filter is used with two arbitrary sampling rate converters. This system can be used for both the continuous increase as well as decrease of the effective bandwidth of a filter. The low complexity and sharpness are achieved by using the frequency-response masking (FRM) approach for the design of the fixed length FIR filter. The sharp transition width leads to maximum rejection to channel interference in SDR.
Clinical expert round table discussion (session 1) at the Margaux Conference on Critical Illness: innate immunity: host recognition of and sensitivity to bacterial components.

Polymorphisms in patients with sepsis is one of the exciting areas of investigation at present. The question remains, however, which kind of polymorphism one ought to look at first or which is more important than the other. Prof. Jean-Paul Mira pointed out that one aspect is to understand why you are looking for polymorphisms and why your patients will have a different phenotype as a result. Of all the patients who develop severe sepsis, only some will develop septic shock. Thus, it would be interesting to compare a group of patients with severe sepsis to a group with septic shock to understand how their inflammatory responses differ. Similarly, it would be interesting to look at DNA chips for patients during the development of septic shock and look for specific gene expression in patients who survive. It is unlikely that there will be a single gene, as Dr. Richard Ulevitch pointed out. There is a spectrum of multiple genes to examine—in both the patient and in the infecting organism—as well as the genetic variation of the organism and its effect on host responses. It is an extremely complex disease situation, but the hope is that 5 yrs from now, DNA chips will profile patients coming into the intensive care unit and offer some prediction of the disease course, and perhaps help guide the treating physician to the appropriate therapies. There probably should be one chip for the genetic background of the host and one for the infecting organisms. Who is developing such chips? The Institute for Systems Biology under the guidance of Dr. Alan Aderem is establishing chips both at the DNA and the protein level that are looking both at expression patterns and the release of proteins from cells. One chip, based on a new method for polymorphism detection, involves heteroduplex formation and permits very rapid scanning. Technology now permits the use of mass spectrometry to perform protein arrays much in the same way that DNA arrays are performed. This technique is extremely useful because many of the molecules that occur during these syndromes are posttranscriptionally regulated so that DNA analysis is insufficient. With regard to which genes are important, Dr. Ulevitch reported on a patient of a colleague with an unidentified hyporesponsive mutation that probably holds the key to an important molecule in innate immune responses. Dr. Bruce Beutler pointed out that in the field of immunity, there is a large role for forward genetics to play, which would allow identification of important mutations. Subsequent reproduction of these mutations in mice would then permit further studies.
Dengue infection in Thai children: a pathophysiological study.

The physiological disturbance in Thai haemorrhagic fever begins with the virus or its products affecting the capillaries: the permeability of the capillary walls increases and the tourniquet test becomes positive. The erythrocytes can pass through the injured capillary walls to produce petechiae, purpura and ecchymoses on the skin and also haemorrhage in the internal organs. Involvement of the liver causes slight elevation of serum transaminases and slight enlargement of the liver. Involvement of the bone marrow causes arrest of the maturation of the megakaryocytes, thus producing thrombocytopenia. Since the virus could rarely be isolated after shock or after the fourth day of disease and since the immunity response was very quick, it is probable that the virus dies after the fourth day of disease. Dying virus or its products may produce an endotoxin-like substance that causes constriction of the
Multiple endocrine neoplasia syndrome: genetic basis for clinical management

Purpose of review Multiple endocrine neoplasia (MEN) types 1 and 2 are rare hereditary cancer syndromes expressing a variety of mainly endocrine neoplasias. Improved understanding of the molecular and clinical genetics associated with these lesions will likely enhance the diagnosis and treatment of patients with these diseases. Recent findings The MEN1 gene causing MEN1 is a tumor suppressor gene and seems to act as a regulator of the transcriptional machinery. Novel genetic and diagnostic modalities tend to identify neoplastic lesions at an earlier stage, potentially improving outcome and quality of life. Improved understanding of genotype-phenotype correlations in MEN2, caused by a mutation in the RET oncogene, may enable a more individualized treatment for these patients. Summary Recent advances in molecular pathology, diagnosis, and management of patients with MEN1 and MEN2 are reviewed.
The use of behavioural change techniques in the treatment of paediatric obesity: qualitative evaluation of parental perspectives on treatment.

BACKGROUND Treatment for childhood obesity is characterized by nonattendance and widespread failure to achieve weight maintenance. The use of behavioural change methods is suggested for engaging families in changing lifestyles. Qualitative methods may improve understanding of patient perceptions, thus improving treatment. The present study aimed to explore the thoughts and feelings of parents whose children had undertaken dietetic consultations either employing behavioural change techniques or delivered by dietitians with no formal training in these techniques. METHODS The study used purposive sampling, interviewing 17 parents of children attending 6-month outpatient treatments for obesity (body mass index > 98 th percentile). Parent's perceptions of the dietetic treatment were explored by in-depth interviews and analysed using Framework methods. RESULTS Parents who had taken part in the behavioural change techniques applauded the process, finding it child-friendly and talked of 'forming a partnership'. Conversely, standard care treatment was less well received. Developing a rapport with the dietitian was significant for the parents in their perception of a positive experience. CONCLUSIONS The present study may help inform future treatments for childhood obesity by providing insights into the aspects of treatment and approaches applauded by parents. It highlights the possible value of use of behavioural change skills by dietitians to engage with families of obese children.
Costs optimization in anaesthesia.

OBJECTIVES The aim of this study is to analyze the direct cost of different anaesthetic techniques used within the Author's hospital setting and compare with costs reported in the literature. METHODS Mean cost of drugs and devices used in our local Department of Anaesthesia was considered in the present study. All drugs were supplied by the in-house Pharmacy Service of Parma's General Hospital. All calculation have been made using an hypothetical ASA1 patient weighting 70 kg. The quality of consumption and cost of inhalation anaesthesia with sevoflurane or desflurane at different fresh gas flow were analyzed, and the cost of total venous anaesthesia (TIVA) using propofol and remifentanil with balanced anaesthesia were also analyzed. In addition, direct costs of general, spinal and sciatic-femoral nerve block anaesthesia used for common plastic surgery procedures were assessed. RESULT The results of our study show that the cost of inhalational anaesthesia decreases using fresh gas flow below 1L, and the use of desflurane is more expensive. In our Hospital, the cost of TIVA is more or less equivalent to the costs of balanced anaesthesia with sevoflurane in surgical procedure lasting more than five hours. The direct cost was lower for the spinal anaesthesia compared with general anaesthesia and sciatic- femoral nerve block for some surgical procedures. (www.actabiomedica.it).
Multivalent antibody fragments with high functional affinity for a tumor-associated carbohydrate antigen.

We report in this work a human-derived self-assembling polypeptide based on the tetramerization domain of the human transcription factor p53, which can be fused to single-chain Fv Ab (scFv) fragments via a long and flexible hinge sequence of human origin, allowing exploitation of the functional affinity increase of binding to a ligand or cell surface with multimeric binding sites. We have demonstrated the use of this polypeptide by applying it to the construction of a tetrameric scFv against the tumor-associated carbohydrate Ag Lewis Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3] GlcNAc beta 1-->3R). For comparison purposes, the corresponding scFv and dimeric mini-antibody, comprising the scFv fused via a flexible murine hinge to an artificial dimerization domain, were also created. The recombinant mini-antibody proteins were expressed in functional form in Escherichia coli and showed the expected m.w. of a dimer and tetramer, respectively. Analysis of Lewis Y-binding behavior by surface plasmon resonance revealed specific but very weak binding of the scFv fragment. In contrast, both dimeric and tetrameric scFv fusion proteins exhibited an enormous gain in functional affinity that was greatest in the case of the tetrameric mini-antibody.
Thermal conductivity of disordered harmonic solids.

As a crystal is disordered, a point may be reached where the typical mean free path of phonons is so short that the wavelength and mean free path are no longer sharp concepts, and the textbook phonon-gas model for thermal conductivity breaks down. This paper proposes an alternate theory for the disordered regime, and the subsequent paper implements the theory for a realistic model of amorphous silicon. The idea is that the dominant scattering is correctly described by a harmonic Hamiltonian, which is, in principle, transformable into a one-body problem of decoupled oscillators. From this the thermal conductivity can be exactly calculated by an analog of the Kubo-Greenwood formula for electrical conductivity of disordered metals
Scratching Beneath the Surface: New Insights into the Functional Properties of the Lateral Occipital Area and Parahippocampal Place Area

We used fMRI on neurologically intact humans to investigate whether or not there are different neural substrates for the different kinds of information that a visual surface signals (shape from texture vs material properties from texture). Participants attended to differences in the shape (flat/convex), texture and color (wood/rock), or material properties (soft/hard) of a set of circular surfaces. Attending to shape activated the contour-sensitive lateral occipital (LO) area, and attending to texture activated a region of the collateral sulcus (CoS) that overlaps with the parahippocampal place area (PPA). Interestingly, attending to material properties activated the same texture-sensitive region in the CoS. These results demonstrate the existence of different neural substrates for the different types of information that a visual surface signals. With regard to object shape, the organization of the LO area may be complex, with neurons tuned not only to the outline shape of objects, but also to their surface curvature independent of contour. Moreover, to our knowledge, this is the first study to demonstrate that processing surface texture, which occurs within the scene-sensitive PPA, is a route to accessing knowledge about an object's material properties. With this in mind, we propose that models of visual cortical organization should focus not only on the particular stimulus category to which a region maximally responds (e.g., objects, scenes), but also on the stimulus attributes that best support the processing of that category (e.g., shape, texture, material properties).
Nutritional Cues Control Pseudomonas aeruginosa Multicellular Behavior in Cystic Fibrosis Sputum

ABSTRACT The sputum (mucus) layer of the cystic fibrosis (CF) lung is a complex substrate that provides Pseudomonas aeruginosa with carbon and energy to support high-density growth during chronic colonization. Unfortunately, the CF lung sputum layer has been difficult to mimic in animal models of CF disease, and mechanistic studies of P. aeruginosa physiology during growth in CF sputum are hampered by its complexity. In this study, we performed chromatographic and enzymatic analyses of CF sputum to develop a defined, synthetic CF sputum medium (SCFM) that mimics the nutritional composition of CF sputum. Importantly, P. aeruginosa displays similar phenotypes during growth in CF sputum and in SCFM, including similar growth rates, gene expression profiles, carbon substrate preferences, and cell-cell signaling profiles. Using SCFM, we provide evidence that aromatic amino acids serve as nutritional cues that influence cell-cell signaling and antimicrobial activity of P. aeruginosa during growth in CF sputum.