Miracle-dz/UniFAR-FTUs huggingface dataset:
Unveiling the Synergistic Interaction Between Liposomal Amphotericin B and Colistin

Patients with multiple comorbidities are often administered simultaneously or sequentially antifungals and antibacterial agents, without full knowledge of the consequences of drug interactions. Considering the clinical relevance of liposomal amphotericin B (L-AMB), the association between L-AMB and six antibacterial agents was evaluated against four clinical isolates and one type strain of Candida spp. and two clinical isolates and one type strain of Aspergillus fumigatus. In order to evaluate such combined effects, the minimal inhibitory concentration (MIC) of L-AMB was determined in the presence of 0.5-, 1-, 2-, and 4-fold peak plasma concentrations of each of the antibacterial drugs. Since the L-AMB/colistin (CST) association was the most synergic, viability assays were performed and the physiological status induced by this association was characterized. In addition, computational molecular dynamics studies were also performed in order to clarify the molecular interaction. The maximum synergistic effect with all antibacterial agents, except CST, was reached at fourfold the usual peak plasma concentrations, resulting in 2-to 8-fold L-AMB MIC reduction for Candida and 2-to 16-fold for Aspergillus. For CST, the greatest synergism was registered at peak plasma concentration (3 mg/L), with 4-to 8-fold L-AMB MIC reduction for Candida and 16-to 32-fold for Aspergillus. L-AMB at subinhibitory concentration (0.125 mg/L) combined with CST 3 mg/L resulted in: a decrease of fungal cell viability; an increase of cell membrane permeability; an increase of cellular metabolic activity soon after 1 h of exposure, which decreased until 24 h; and an increase of ROS production up to 24 h. From the molecular dynamics studies, AMB and CST molecules shown a propensity to form a stable molecular complex in solution, conferring a recognition and binding added value for membrane intercalation. Our results demonstrate that CST interacts synergistically with L-AMB, forming a stable complex, which promotes the fungicidal activity of L-AMB at low concentration.
Channel-optimized vector quantization with mutual information as fidelity criterion

We consider the problem of channel-optimized vector quantization (COVQ) with mutual information as fidelity criterion. This problem is relevant in a communications context, where the goal is to maximize the end-to-end rate. We propose an algorithm which is similar to the information bottleneck method and solves the considered COVQ problem. In contrast to existing COVQ designs, the proposed method implicitly optimizes the labels of the quantizer outputs, thereby avoiding separate label optimization. The usefulness of the proposed method is corroborated by application examples and numerical results.
Using the Fast Fourier Transform to Accelerate the Computational Search for RNA Conformational Switches

Using complex roots of unity and the Fast Fourier Transform, we design a new thermodynamics-based algorithm, FFTbor, that computes the Boltzmann probability that secondary structures differ by base pairs from an arbitrary initial structure of a given RNA sequence. The algorithm, which runs in quartic time and quadratic space , is used to determine the correlation between kinetic folding speed and the ruggedness of the energy landscape, and to predict the location of riboswitch expression platform candidates. A web server is available at http://bioinformatics.bc. edu/clotelab/FFTbor/.
Filament stretching and capillary breakup extensional rheometry measurements of viscoelastic wormlike micelle solutions

A filament stretching extensional rheometer and capillary breakup extensional rheometer are used to measure the extensional rheology of a series of wormlike micelle solutions experiencing a uniaxial elongational flow. The experiments are performed using a series of wormlike micelle solutions of both cetylpyridinium chloride and sodium salicylate (NaSal) in an aqueous sodium chloride solution and cetyltrimethylammonium bromide and NaSal in de-ionized water. The linear viscoelasticity of all the wormlike micelle solutions is well described by a Maxwell model with just one or two relaxation times while the steady shear measurements all demonstrate characteristics of shear banding at large shear rates. In transient homogeneous uniaxial extension imposed by a filament stretching rheometer, each of the wormlike micelle solutions demonstrate significant strain hardening. At large extension rates, the wormlike micelle solution filaments are all found to fail through a dramatic rupture near the axial midplane at a constant stress independent of imposed extension rate. The result is an extensional viscosity that decays linearly with increasing extension rate. This filament failure likely stems from the local scission of individual wormlike micelle chains. For the more concentrated solutions, as the imposed extension rate is reduced, a critical extension rate is found below which the filament does not rupture, but instead elastocapillary pinch off is recovered and the elastic tensile stresses achieved in the fluid filament grow far beyond the value observed at rupture. This dramatic upturn in the elastic tensile stress and the extensional viscosity at low extension rates is not intuitively expected and is most likely a result of structural changes to the entangled wormlike micelle solution. Strain hardening is also observed in capillary breakup rheometry experiments, however, when the results of filament stretching and capillary breakup rheometry measurements at nominally the same extension rate are superimposed, the results do not agree; the extensional viscosity measurements from filament stretching are in some instances more than an order of magnitude larger. This result calls into question the use of capillary breakup rheometry for quantitatively measuring the extensional viscosity of wormlike micelle solutions.
Insulin-Like Growth Factor Binding Protein-2: Contributions of the C-Terminal Domain to Insulin-Like Growth Factor-1 Binding

Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them attractive candidates as therapeutics for cancer prevention and control. Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition, respectively). We previously identified IGF-1 contact sites both upstream and downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem276:2880-2889, 2001). To further test their contributions to IGFBP-2 function, the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2-(2′nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS-skatole products IGFBP-21-248 and IGFBP-2249-289 as well as IGFBP-21-190 were expressed as glutathione S-transferase-fusion proteins and purified. Based on competition binding analysis, deletion of residues 249 to 289 caused an ∼20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM and IGFBP-21-248 = 7 nM). Removal of the remainder of the C-terminal domain had no further effect on affinity (IGFBP-21-190 EC50 = 9.2 nM). In kinetic assays, IGFBP-21-248 and IGFBP-21-190 exhibited more rapid association and dissociation rates than full-length IGFBP-2. These results confirm that regions upstream and downstream of the CWCV motif participate in IGF-1 binding. They further support the development of full-length IGFBP-2 as a cancer therapeutic.
The assimilation of Irish immigrants in Englande

Remarkably little is known about the processes and extent of educational and occupational assimilation, convergence of social mobility experiences and patterns of intermarriage of England's largest immigrant community, the Irish. In this paper assimilation is regarded as a process in which both cultural and structural differences between the immigrant group and the indigenous population are progressively reduced over an extended period of time. Using nationally representative data from the General Household Surveys of 1979 and 1980, first and second generation immigrants from the Republic of Ireland and Northern Ireland were compared with a tontrol sample of'English', with all analyses run separately for men and women. It is concluded that, while there is generally a substantial measure of assimilation of the Irish in England by the second generation, there are important differences between immigrants from the Republic of Ireland and Northern Ireland - the former showing much higher levels of educational and occupational
Antimicrobial Actions of Reactive Oxygen Species

ABSTRACT Everything should be as simple as it can be, but not simpler. —Attributed to Albert Einstein (1) IMPORTANCE Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in Salmonella-phagocyte interactions and attempts to reconcile conflicting observations from different laboratories.
Ethnic Jokes, Moral Values and Social Boundaries

The universal popularity of ethnic jokes and in particular those about supposedly 'stupid' or 'crafty' ethnic minorities is to be explained in terms of the general characteristics of industrial societies rather than the particular circumstances of each separate society. The ethnic jokes of western industrial societies in both peacetime and wartime reflect the competing moral values, uncertain social boundaries and impersonal power structures of these societies. The corresponding eastern European jokes are in some respects similar but as one might expect highly politicized and reflect the deeper social and political divisions that characterize the socialist industrial countries. Ethnic jokes delineate the social, geographical and moral boundaries of a nation or ethnic group. By making fun of peripheral and ambiguous groups they reduce ambiguity and clarify boundaries or at least make ambiguity appear less threatening. Ethnic jokes occur in opposed pairs such as those mocking 'st-upid' and 'crafty', or 'cowardly' and 'militaristic' groups respectively and express the problems and anxieties caused by the conflicting norms and values inevitably found in large societies dominated by anomic impersonal institutions such as the market place and bureaucracy.
Compartment‐specific regulation of plasma membrane calcium ATPase type 2 in the chick auditory brainstem

Calcium signaling plays a role in synaptic regulation of dendritic structure, usually on the time scale of hours or days. Here we use immunocytochemistry to examine changes in expression of plasma membrane calcium ATPase type 2 (PMCA2), a high‐affinity calcium efflux protein, in the chick nucleus laminaris (NL) following manipulations of synaptic inputs. Dendrites of NL neurons segregate into dorsal and ventral domains, receiving excitatory input from the ipsilateral and contralateral ears, respectively, via nucleus magnocellularis (NM). Deprivation of the contralateral projection from NM to NL leads to rapid retraction of ventral, but not the dorsal, dendrites of NL neurons. Immunocytochemistry revealed symmetric distribution of PMCA2 in two neuropil regions of normally innervated NL. Electron microscopy confirmed that PMCA2 localizes in both NM terminals and NL dendrites. As early as 30 minutes after transection of the contralateral projection from NM to NL or unilateral cochlea removal, significant decreases in PMCA2 immunoreactivity were seen in the deprived neuropil of NL compared with the other neuropil that continued to receive normal input. The rapid decrease correlated with reductions in the immunoreactivity for microtubule‐associated protein 2, which affects cytoskeleton stabilization. These results suggest that PMCA2 is regulated independently in ventral and dorsal NL dendrites and/or their inputs from NM in a way that is correlated with presynaptic activity. This provides a potential mechanism by which deprivation can change calcium transport that, in turn, may be important for rapid, compartment‐specific dendritic remodeling. J. Comp. Neurol. 514:624–640, 2009. © 2009 Wiley‐Liss, Inc.
CD30 Is Dispensable for T-Cell Responses to Influenza Virus and Lymphocytic Choriomeningitis Virus Clone 13 but Contributes to Age-Associated T-Cell Expansion in Mice

CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin’s disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses. We show that CD30 is expressed on activated but not resting CD4 and CD8 T cells in vitro, as well as on regulatory T cells and marginally on T helper 1 cells in vivo during influenza infection. Despite this, CD4 and CD8 T-cell expansion in response to influenza virus was comparable in CD30+/+ and CD30−/− littermates, with no discernable role for the pathway in the outcome of influenza infection. Similarly, during persistent infection with LCMV clone 13, CD30 plays no obvious role in CD4 or CD8 T-cell responses, the level of T-cell exhaustion or viral control. In contrast, in the steady state, we observed increased numbers of total CD4 and CD8 T cells as well as increased numbers of regulatory T cells in unimmunized older (~8 months) CD30+/+ but not in CD30−/− age-matched littermates. Naive T-cell numbers were unchanged in the aged CD30+/+ mice compared to their CD30−/− littermate controls, rather the T-cell expansions were explained by an increase in CD4+ and CD8+ CD44mid-hiCD62L− effector memory cells, with a similar trend in the central memory T-cell compartment. In contrast, CD30 did not impact the numbers of T cells in young mice. These data suggest a role for CD30 in the homeostatic regulation of T cells during aging, contributing to memory T-cell expansions, which may have relevance for CD30 expression in human T-cell lymphoproliferative diseases.
Help-seeking process of parents for psychopathology in youth with moderate to borderline intellectual disabilities.

OBJECTIVE To study the help-seeking process of parents for emotional or behavioral problems in their child with borderline to moderate intellectual disabilities. METHOD In 2003, in a special education-based sample of 522 youths (ages 10-18 years, response = 77.9%), we studied the parents' perception of their child's problems, their subsequent felt need for professional help, actual help-seeking, and the factors possibly related to taking these steps. RESULTS Even when parents indicated their child's emotional or behavioral functioning as "neither good nor bad," in about 70%, these problems were present according to standardized measures. Of the 213 parents (40.8%) who perceived problems, 70.6% felt a need, and 55.2% of these parents subsequently sought professional help. Parents more often sought help when their child had problems of anxiety and depression, experienced negative life events, and when parents perceived child psychopathology before the past year. Reported barriers to seeking help predominantly related to parents' evaluation of the severity of these problems and wanting to solve the problems themselves. CONCLUSIONS Clinicians and other service providers should address parents' concerns regarding their child's emotional/behavioral functioning and treatment seeking. Also, they should provide information on treatment options and on signs and potential negative prospects of their child's problems.
A Significant Role for Histocompatibility in Human Islet Transplantation

Background. In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation. Methods. We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-γ and interleukin-2. Results. Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets Conclusion. Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.
Three-years clinical outcome of immediate provisionalization of single Osseospeed(™) implants in extraction sockets and healed ridges.

AIM The purpose of this prospective multicenter clinical study was to compare 3 years implant survival, bone and soft tissue changes following immediate loading using single Osseospeed(™) implants (Astra Tech AB, Mölndal, Sweden) installed in healed ridges or extraction sockets. MATERIAL AND METHODS Implants were provisionally restored the day of surgery using cemented acrylic crowns out of full occlusion. The provisional crowns were replaced after 12 weeks by full-ceramic crowns. Implant survival, bone levels, soft tissue levels and peri-implant health were monitored up to 3 years. RESULTS 55 patients (22 men, 33 women; mean age 45) had the implant installed in extraction sockets and 58 patients (25 men, 33 women; mean age 42) received conventional implant treatment in healed ridges. Three implants failed in the extraction group and one implant failed in the healed group, all failures occurred before the final crown placement. No further losses occurred during 3 years, giving a statistically comparable survival rate of 94.6% and 98.3%, respectively. The total bone loss after 3 years, compared to implant placement was 0.4 mm (SD 1.5) in healed sites, whilst the immediate sites showed a bone gain of 1.6 mm (SD 2.4) due to bone fill in the alveolus. Papillae retracted with 0.3 and 0.0 mm in the period of provisionalization, but grew back after final crown was placed with 0.3 and 0.5 mm in extraction and healed sites respectively after 3 years. Plaque and inflammation scores were very low throughout the study time, irrespective of treatment modality. CONCLUSIONS Immediate implants restored at the day of surgery show comparable risk for implant failure, bone loss and midfacial soft tissue recession compared to conventionally installed implants. The 3-years results suggest both hard and soft tissue stability.
Modeling video traffic in the wavelet domain

A significant discovery from this work is that although video traffic has complicated short- and long-range dependence in the time domain, the corresponding wavelet coefficients are no longer long-range dependent in the wavelet domain. Therefore, a "short-range" dependent process can be used to model video traffic in the wavelet domain. In this work, we develop such wavelet models for VBR video traffic. The strength of the developed wavelet models includes: (1) it provides a unified approach to model both long-range and short-range dependence in video traffic simultaneously, (2) it has the ability to reduce the temporal dependence so significantly that the wavelet coefficients can be modeled by either independent or Markov models, and (3) the model results in a computationally efficient method on generating high quality video traffic.
Thyroid Hormones in Human Milk and their Influence on Thyroid Function of Breast-Fed Babies

Summary: Various assay methods for detection of thyroid hormones in human milk were evaluated in recovery and dilution experiments after which the concentrations of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were measured and compared with those in serum. The effect of breast feeding on pituitary thyroid function of normal babies also was studied. Competitive protein-binding analysis (CPBA) was found to be unsuitable for measurement of T4 in milk. T4 was not detected in samples of human milk by four radioimmunoassays (RIA), although more than 100% of T4 was recovered in the assays. RIA (double antibody-ANS system) seemed to be reliable for detection of T3 in milk, judging from recovery and dilution experiments. T3 was detectable in all samples obtained 1–4 months postpartum. The T3 concentration in milk was not correlated with protein concentration or daily volume. The concentration of T3 in milk was lower than that in serum and the mean ratio of serum T3 to milk T3 was 2.8 ± 1.7 (mean ± S.D.). No correlation was observed between the T3 concentration or daily T3 excretion in milk and the T3 concentration in serum. The total amount of T3 excreted in milk was estimated as only 5–1000 ng/day. The serum levels of thyrotropin, T4, free T4 and T3 were not significantly different between breast-fed and bottle-fed babies. These results indicate that T3 excretion in milk cannot be explained by simple diffusion from the blood into the mother's milk and that breast feeding has no influence on the pituitary thyroid axis of normal babies.
The National General Practice Study of Epilepsy. The syndromic classification of the International League Against Epilepsy applied to epilepsy in a general population.

In this prospective, population-based study of 594 cases of newly diagnosed epilepsy, proportions in categories as defined by the International League Against Epilepsy (ILAE) were as follows: (1) localization-related epilepsies: 1.1* idiopathic, 1.2%; 1.2* symptomatic, 16.2%; and 1.3 cryptogenic, 24.6%; (2) generalized epilepsies: 2.1* idiopathic (idiopathic generalized epilepsy) with 3-Hz spike and wave: absence epilepsy, 2.2%; juvenile myoclonic epilepsy, 1.5%; and nonspecific idiopathic generalized epilepsy, 5.6%; 2.3. 1* symptomatic generalized epilepsies, 1.5%; 2.3.2* specific syndromes with generalized epilepsy, 0.3%; 3.2 seizures without unequivocal focal or generalized features, 32%; 4.1 situation-related syndromes, isolated seizures, 9.9%; seizures due to acute toxic or metabolic cause,* 4.5%. Only 33.6% were in diagnostic ILAE categories (asterisks) and many rare syndromes were not represented. The remainder (66.4%) were in various nonspecific categories. Only 24% of localization-related epilepsies could be clinically localized to a single ILAE-proposed site of origin and of these best localized cases, 14% had strongly discordant imaging or electroencephalograms. These major problems in applying the ILAE classification to epilepsy in the general population and its underemphasis of modern imaging techniques are discussed.