Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydration of a hydrophobic cavity and its functional role: A simulation study of human interleukin‐1β

Molecular dynamics simulations reveal that the hydrophobic cavity in human cytokine Interleukin‐1β is hydrated and can dynamically accommodate between one and four water molecules. These waters have residence times >> 500 ps and can give rise to detectable NOEs, in agreement with NMR observations of Ernst et al. (Science 1995; 267:1813–1817). The waters also display high positional disorder within the cavity, which explains why they have not been resolved crystallographically. The average distribution of water molecules over time within the cavity matches well the low resolution electron density extracted by Yu et al. (Proc Natl Acad Sci 1999; 96:103–108). The water molecules hydrate the hydrophobic cavity preferentially as complex clusters. These clusters result from a combination of hydrogen bonds between the waters and stabilizing interactions between the waters and aromatic rings forming the cavity. Free energy estimates suggest that it takes 4‐waters to hydrate the cavity in a thermodynamically stable manner leading to a gain in free energy of transfer from bulk of ∼∼3.6 kcal/mol. This arises from the existence of the water clusters in multiple hydrogen bonded states. In addition, the waters are found to migrate either individually or as clusters out of the cavity through several pathways. The upper limit for one‐dimensional diffusion of the waters within the protein matrix is 4 Å/ps (relative to 6 Å/ps for bulk). Simulations reveal pathways in addition to those identified crystallographically, with motions controlled by the rotations of sidechains. We find that only when the hydrophobic cavity is hydrated, do correlated motions couple distant sites with the sites that make contact with the receptor and this data partly offers an explanation of experimental mutagenesis data. Simulations, together with recent observations based on mutagenesis by Heidary et al. (J Mol Biol 2005; 353:1187–1198) that hydrogen bond networks couple motions across long distances in interleukin‐1 β, lead us to hypothesize that the hydration of the cavity (conserved across mammals) can thermodynamically enhance hydrogen bond networks to enable coupling across long distances by acting as a plug and this in turn enables a kinetic control of the rate of transmission of signals. Proteins 2007. © 2007 Wiley‐Liss, Inc.
The Global Flow of Hard Disk Drives: Quantifying the Concept of Value Leakage in E‐waste Recovery Systems

The remaining value within end‐of‐use/life hard disk drives (EoU/L HDDs) is often not optimally recovered. The improper collection and recovery of HDDs contribute not only to rising environmental and social concerns worldwide, but also to the transformation of the economy and a significant loss of value. Currently, the most preferred treatment option for used hard drives is to recover the metals with the highest recycling effectiveness, such as steel and aluminum, via a shredding‐based recycling process that results in both value and material leakages. The complexity of retrieving the remaining values within EoU/L HDDs demands a larger view of the global supply of HDDs available for recovery. The aim of this paper is to first identify the geographical patterns of transboundary global shipments of new and used HDDs between developing and developed regions, and then capture and quantify the value leakage by bringing several unique perspectives. Two analyses have been conducted. First, the loss of value due to the insufficient recovery of neodymium (Nd) at the global level is quantified. Second, the value leakage as a result of the delay on on‐time reuse of HDDs is captured. Furthermore, the central challenges toward proper recovery of HDDs, where consumer electronic industry can make significant contributions, have been identified. HDDs are well positioned to contribute important insights to the recovery of other electronic devices, so the findings from HDDs can be adopted for other types of electronics.
Brain-derived Neurotrophic Factor-induced Potentiation of Ca2+ Oscillations in Developing Cortical Neurons*

Brain-derived neurotrophic factor (BDNF) has been reported to exert an acute potentiation of synaptic activity. Here we examined the action of BDNF on synchronous spontaneous Ca2+ oscillations in cultured cerebral cortical neurons prepared from postnatal 2–3-day-old rats. The synchronous spontaneous Ca2+ oscillations began at approximately DIV 5. It was revealed that voltage-dependent Ca2+ channels and ionotropic glutamate receptors were involved in the synchronous spontaneous oscillatory activity. BDNF potentiated the frequency of these oscillations. The BDNF-potentiated activity reached 207 ± 20.1% of basal oscillatory activity. NT-3 and NT-4/5 also induced the potentiation. However, nerve growth factor did not. We examined the correlation between BDNF-induced glutamate release and the BDNF-potentiated oscillatory activity. Both up-regulation of phospholipase C-γ (PLC-γ) expression and the BDNF-induced glutamate release occurred at approximately DIV 5 when the BDNF-potentiated oscillations appeared. We confirmed that the BDNF-induced glutamate release occurred through a glutamate transporter that was dependent on the PLC-γ/IP3/Ca2+ pathway. Transporter inhibitors blocked the BDNF-potentiated oscillations, demonstrating that BDNF enhanced the glutamatergic transmissions in the developing cortical network by inducing glutamate release via a glutamate transporter.
Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections

Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2–3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron. (ABSTRACT TRUNCATED AT 250 WORDS)
The Role of Parents on the Home Ownership Experience of Their Children: Evidence from the Health and Retirement Study

We construct matched panel data sets of adult children with their parents to study the role of lagged parental attributes on subsequent home ownership decisions between 2000 and 2012. Earlier research has demonstrated intergenerational wealth transfers from parents to children are an important source of upfront equity used to purchase a first home, although parental attributes are often omitted as determinants of tenure due to data limitations. A significant role is found for lagged parental wealth on the ability of adult children to become and remain home owners over this period. Endowed differences in parental wealth are estimated to account for the largest explainable share of the white/non-white gap in becoming a homeowner, and maintaining home ownership once attained.
Production of reactive oxygen species by hemocytes from the cattle tick Boophilus microplus.

We have investigated the phagocytic activity and the production of reactive oxygen species (ROS) by hemocytes from the cattle tick Boophilus microplus. Two main types of hemocytes were detected in tick hemolymph: plasmatocytes and granulocytes. The plasmocytes were the most abundant cells, being responsible for the in vivo phagocytosis of yeast. ROS production was evaluated by luminol-amplified luminescence and phenol red oxidation. The luminescence increased when hemocytes were incubated with bacteria, zymosan, or phorbol 12-miristate 13-acetate (PMA). The luminescence was inhibited by superoxide dismutase and catalase, which are antioxidant enzymes that remove superoxide and hydrogen peroxide, respectively. The phenol red oxidation assay also showed an increase in the level of hydrogen peroxide produced by hemocytes stimulated with bacteria and PMA. Taken all together, our data indicate that tick hemocytes are able to produce ROS during the phagocytic process similarly to vertebrate phagocytes.
Probiotics as prevention and treatment for diarrhea

Purpose of review To critically appraise evidence on probiotic use for prevention and treatment of diarrhea in children and adults. Recent findings Several randomized controlled trials and meta-analyses suggested that probiotics are effective in primary and secondary prevention of gastroenteritis and its treatment. Selected Lactobacillus strains had a modest, although significant effect in primary prevention. Saccharomyces boulardii was effective in antibiotic-associated and in Clostridium difficile diarrhea. There is evidence that it might prevent diarrhea in day-care centers. Lactobacillus rhamnosus GG was associated with reduced diarrheal duration and severity, more evident in case of childhood Rotavirus diarrhea. Similar, although weaker, evidence was obtained with S. boulardii. Both strains are included in evidence-based recommendations for gastroenteritis management in children. Data on other Lactobacillus strains are preliminary. Probiotic efficacy was related to cause, early administration and bacterial load, and their mechanisms were associated with antiinfectious action in the intestine or, indirectly, to modulation of innate and adaptive immunity. Summary Probiotics have gained a role as adjunctive treatment of infantile gastroenteritis together with rehydration. Their efficacy is less convincing in adults, but promising in antibiotic-associated diarrhea. However, evidence of efficacy is limited to a few strains.
Identification and Characterization of Multiple Osmotic Response Sequences in the Human Aldose Reductase Gene*

Aldose reductase (AR) has been implicated in osmoregulation in the kidney because it reduces glucose to sorbitol, which can serve as an osmolite. Under hyperosmotic stress, transcription of this gene is induced to increase the enzyme level. This mode of osmotic regulation of AR gene expression has been observed in a number of nonrenal cells as well, suggesting that this is a common response to hyperosmotic stress. We have identified a 132-base pair sequence ∼1 kilobase pairs upstream of the transcription start site of the AR gene that enhances the transcription activity of the AR promoter as well as that of the SV40 promoter when the cells are under hyperosmotic stress. Within this 132-base pair sequence, there are three sequences that resemble TonE, the tonicity response element of the canine betaine transporter gene, and the osmotic response element of the rabbit AR gene, suggesting that the mechanism of osmotic regulation of gene expression in these animals is similar. However, our data indicate that cooperative interaction among the three TonE-like sequences in the human AR may be necessary for their enhancer function.
Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions

The broadly neutralizing anti-HIV antibody 4E10 recognizes an epitope very close to the virus membrane on the glycoprotein gp41. It was previously shown that epitope recognition improves in a membrane context and that 4E10 binds directly, albeit weakly, to lipids. Furthermore, a crystal structure of Fab 4E10 complexed to an epitope peptide revealed that the centrally placed, protruding H3 loop of the antibody heavy chain does not form peptide contacts. To investigate the hypothesis that the H3 loop apex might interact with the viral membrane, two Trp residues in this region were substituted separately or in combination with either Ala or Asp by site-directed mutagenesis. The resultant IgG variants exhibited similar affinities for an epitope peptide as WT 4E10 but lower apparent affinities for both viral membrane mimetic liposomes and Env(−) virus. Variants also exhibited lower apparent affinities for Env(+) virions and failed to significantly neutralize a number of 4E10-sensitive viruses. For the extremely sensitive HXB2 virus, variants did neutralize, but at 37- to >250-fold lower titers than WT 4E10, with Asp substitutions exerting a greater effect on neutralization potency than Ala substitutions. Because reductions in lipid binding reflect trends in neutralization potency, we conclude that Trp residues in the antibody H3 loop enable membrane proximal epitope recognition through favorable lipid interactions. The requirement for lipophilic residues such as Trp adjacent to the antigen binding site may explain difficulties in eliciting 4E10-like neutralizing antibody responses by immunization and helps define a unique motif for antibody recognition of membrane proximal antigens.
MPEG compression of ultrasound RF channel data for a real-time software-based imaging system

Using software for beamforming in ultrasound systems provides high flexibility, and the large number of computations required in a software-based system can be performed in real time on a PC. However, the very large data transfer rate required from the ultrasound front-end to the PC host for real-time operation is a bottleneck which cannot be overcome without appropriate compression. Previous studies have examined JPEG compression of ultrasound RF channel data, but the schemes do not exploit temporal redundancy between adjacent frames. This study utilized MPEG technology to process the ultrasound RF data to increase the compression efficiency. Our results indicate that MPEG compression generally provides a better compression ratio than does JPEG compression. As an example, the compression ratio of MPEG compression in an 8-bit channel A/D data under 5 μm interframe displacement is smaller than 0.13, thus allowing real-time data transfer requirements to be met. Moreover, the compression efficiency for motions in different directions is shown to be highly dependent on the frame-to-frame correlation.
Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes

ABSTRACT Exposure to carcinogenic alkylating agents, oxidizing agents, and ionizing radiation modulates transcript levels for over one third ofSaccharomyces cerevisiae's 6,200 genes. Computational analysis delineates groups of coregulated genes whose upstream regions bear known and novel regulatory sequence motifs. One group of coregulated genes contain a number of DNA excision repair genes (including the MAG1 3-methyladenine DNA glycosylase gene) and a large selection of protein degradation genes. Moreover, transcription of these genes is modulated by the proteasome-associated protein Rpn4, most likely via its binding to MAG1 upstream repressor sequence 2-like elements, that turn out to be almost identical to the recently identified proteasome-associated control element (G. Mannhaupt, R. Schnall, V. Karpov, I. Vetter, and H. Feldmann, FEBS Lett. 450:27–34, 1999). We have identified a large number of genes whose transcription is influenced by Rpn4p.
Inflation Expectations in Turkey: Determinants and Roles in Missing Inflation Targets

Abstract This paper aims at specifying the determinants of 12-month ahead and 24-month ahead inflation expectations in Turkey by using monthly data from April 2006 to December 2016. Put differently, this paper tries to shed light on how inflation expectations respond to changes in past inflation rate, inflation target, output gap, USD/TL exchange rate, oil price, and EMBI in Turkey. To this end, the paper first conducts unit root tests in order to detect the order of integration of the variables. Then, the paper employs the autoregressive distributed lag approach to examine whether there is a cointegration relationship among variables and to estimate long-run parameters. According to the findings, 12-month ahead expected inflation rate is positively related to past inflation rate, inflation target, output gap, USD/TL exchange rate, and oil price and is negatively related to EMBI. Besides, 24-month ahead expected inflation rate is positively related to past inflation rate and USD/TL exchange rate and is negatively related to inflation target and EMBI. Upon its findings, the paper makes some inferences about the success of inflation targeting strategy in Turkey.
Disseminated Mycobacterium avium Complex With Cutaneous Lesions

Background: Although most commonly encountered in patients with human immunodeficiency virus infection, disseminated Mycobacterium avium complex (MAC) is becoming more common in patients receiving immunosuppressive medications. Disseminated MAC with skin lesions may occur, and several presentations have been reported, including panniculitis, cutaneous granulomas, pustules, ulcerations, and erythematous skin lesions. Objectives: The objective of this report is to describe an unusual presentation of MAC that is unlikely to be encountered frequently in the outpatient dermatology setting, especially in a patient without human immunodeficiency virus infection. Methods: The authors present a case of disseminated MAC infection with cutaneous manifestations in an iatrogenically immunocompromised patient. Conclusions: Diagnosis of MAC infection is challenging given the varied clinical presentations and the difficulty in culturing MAC. In addition, the acid-fast stain is nonspecific. Clinicians should remember to consider MAC infection in patients with acid-fast-positive skin lesions, as the selection of appropriate antibiotic therapy is species specific.
Identification and Distribution of Neuroleptic Binding Sites in the Rat Spinal Cord

Abstract: Identification of neuroleptic receptor sites in the rat spinal cord could be achieved by the binding of [3H]haloperidol to membranes taken from the different horns. The use of pooled frozen microdiscs punched from these different spinal cord areas allowed the detection of saturable stereospecific binding, as defined in the presence of (+)‐ and (‐)‐butaclamol. Comparison of the binding constants with those obtained in the corpus striatum resulted in similar dissociation constants and Hill's slopes. Maximal binding capacity was quite different, being the greatest in the whole striatum (157 ± 8 fmol/mg protein) followed by the dorsal horn (56 ± 3 fmol/mg protein) and the lateral (34 ± 5 fmol/mg protein) and ventral ones (31 ± 2 fmol/mg protein). The displacement of the labelled ligand by different dopaminergic and nondopaminergic drugs at various concentrations gave similar results in the whole striatum and the spinal cord, giving further support for the existence of a dopaminergic innervation of the spinal cord and showing that dopaminergic receptor sites are distributed through the different spinal horns, with a maximal density in the dorsal horn–as for dopamine levels. No detectable stereospecific binding could be obtained from the surrounding spinal white matter, even at high tissue concentrations. Owing to poor sensitivity of the binding technique, no stereospecific neuroleptic binding could be demonstrated in the whole spinal cord, even at very high tissue concentration, whereas it could be detected in spinal cord tissue sampled from restricted areas of dense dopaminergic innervation.
Predictors of cessation pharmacotherapy use among black and non-Hispanic white smokers.

INTRODUCTION Use of pharmacotherapy for smoking cessation improves quit rates, but these treatments are underutilized, particularly among Black smokers. Attitudes toward pharmacotherapy may differ between racial/ethnic minorities and Caucasian smokers. It was hypothesized that Black and non-Hispanic White smokers would differ in their attitudes toward pharmacotherapy and that the association between attitudes toward and actual use of pharmacotherapy would differ by race. METHODS The study consisted of a single, cross-sectional telephone-based survey of current smokers (N = 697), which examined the relationship between race, attitudes toward pharmacotherapy, and pharmacotherapy usage in a representative bi-racial sample (39% Black). RESULTS Black smokers were significantly less likely to report ever use of pharmacotherapy (23%) than Caucasians (39%; odds ratio [OR] = 0.46; 95% CI: 0.33-0.66). Compared with Caucasians, Blacks had significantly less favorable attitudes toward pharmacotherapy, including disbelief about efficacy (p = .03), addiction concerns (p = .03), harmfulness of pharmacotherapy (p = .008), and need for treatment of any kind to quit smoking (p = .004). In a multiple logistic regression, racial group (Caucasian is referent: OR = 0.55, p = .003), addiction concerns (OR = 0.80, p < .01), and need for treatment of any kind to quit smoking (OR = 1.52, p < .001) were predictive of pharmacotherapy use. CONCLUSIONS These findings replicate and build upon previous research demonstrating underutilization of pharmacotherapy and enduring misconceptions about pharmacotherapy, particularly among Black smokers. Regardless of racial group, misconceptions about pharmacotherapy are related to lower rates of use. Efforts to improve understanding about the efficacy and safety of these products are needed to boost utilization and impact cessation rates.
Health effects of ozone. A critical review.

Health and pollution control professionals and the general public need to develop a more complete understanding of the health effects of ozone (O3) because: 1) we have been unable to significantly reduce ambient O3 levels using current strategies and controls; 2) in areas occupied by more than half of the U.S. population, current peak ambient O3 concentrations are sufficient to elicit measurable transient changes in lung function, respiratory symptoms, and airway inflammation in healthy people engaged in normal outdoor exercise and recreational activities; 3) the effects of O3 on transient functional changes are sometimes greatly potentiated by the presence of other environmental variables; and 4) cumulative structural damage occurs in rats and monkeys exposed repetitively to O3 at levels within currently occurring ambient peaks, and initial evidence from dosimetry models and interspecies comparisons indicate that humans are likely to be more sensitive to O3 than rats. The extent and significance of these effects, and the multibillion dollar costs of ambient O3 controls need to be considered in any future revisions of ambient standards and the Clean Air Act. The transient effects of O3 are more closely related to cumulative daily exposure than to one hour peak concentrations, and future revisions of the ambient standard for O3 should take this into account. The effects of long-term chronic exposure to O3 remain poorly defined, but recent epidemiologic and animal inhalation studies suggest that current ambient levels are sufficient to cause premature aging of the lungs. More research is needed to determine the need for a standard with a seasonal or annual average concentration limit.