Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza

Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR+ inflammatory chemokine MIP-2 (CXCL2/GRO-β) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza.
On the Stability of Zero Dynamics of a Single-Link Flexible Manipulator for a Class of Parametrized Outputs

In order to correct the misinterpretation which has occurred in two recent works concerning the stability of infinite-dimensional zero dynamics, the stability of zero dynamics of a noncollocated single-link flexible manipulator is considered in this article for a class of outputs containing a constant parameter. The characteristic equation governing the eigenvalues of zero dynamics is derived. The distribution of these eigenvalues on the complex plane (which depends on the values of the constant parameter) can be found analytically by using the methods of infinite product expansion and root locus. The equivalence of the eigenvalues of zero dynamics and the zeros of the transfer function is also verified. © 2003 Wiley Periodicals, Inc.
Conjugating Prussian blue nanoparticles onto antigen-specific T cells as a combined nanoimmunotherapy.

AIM To engineer a novel nanoimmunotherapy comprising Prussian blue nanoparticles (PBNPs) conjugated to antigen-specific cytotoxic T lymphocytes (CTL), which leverages PBNPs for their photothermal therapy (PTT) capabilities and Epstein-Barr virus (EBV) antigen-specific CTL for their ability to traffic to and destroy EBV antigen-expressing target cells. MATERIALS & METHODS PBNPs and CTL were independently biofunctionalized. Subsequently, PBNPs were conjugated onto CTL using avidin-biotin interactions. The resultant cell-nanoparticle construct (CTL:PBNPs) were analyzed for their physical, phenotypic and functional properties. RESULTS Both PBNPs and CTL maintained their intrinsic physical, phenotypic and functional properties within the CTL:PBNPs. CONCLUSION This study highlights the potential of our CTL:PBNPs nanoimmunotherapy as a novel therapeutic for treating virus-associated malignancies such as EBV+ cancers.
EXPLICIT ESTIMATES FROM CAPTURE-RECAPTURE DATA WITH BOTH DEATH AND IMMIGRATION-STOCHASTIC MODEL.

A brief review, with references, of the literature on capture-recapture theory is given in Jolly (1963). More recently, Cormack (1964) gives a solution, including asymptotic variances, for a specific situation involving the marking and release of a non-random sample of fulmar petrels. His model is stochastic and will be referred to in ? 4. Seber (1962, 1965) has also produced some interesting solutions, and these together with Darroch (1958, 1959) are most directly relevant to our present problem. Darroch (1958, 1959) shows that in a fully stochastic model with either immigration (often called dilution) or death (or emigration), the population parameters can be easily estimated by maximum likelihood. For the more general case when death and immigration are operating simultaneously he derives estimation equations by equating certain observations to their expectations, but does not give variances or covariances for the estimates. In a later paper, (Darroch, 1961), he considers estimation for a closed population consisting of different strata. Seber (1962) establishes a stochastic model for what he calls the multi-sample single recapture census in which an individual cannot be recaptured more than once. This situation arises, for example, when the recaptures are made in the course of hunting or fishing. He allows for both death and immigration in the population, provides explicit maximumlikelihood estimates of the parameters with variances, and suggests tests for certain of the assumptions. In a second paper, (Seber, 1965), he considers a multiple-recapture model differing only slightly from that of Darroch (1959), with both death and immigration. Again, he provides explicit maximum-likelihood estimates of the parameters with variances. A test is also given for equi-catchability in a closed population of individuals with different capture histories. The first purpose of the present paper is to derive a general probability distribution designed to fit the majority of capture-recapture problems involving a 'single' population. The word 'single' here denotes a population covering an area within whose boundaries the animals (or, in general, individuals or members) are free to move and to mix with others of their kind, but which is regarded as a single area in respect of which parameters are to be estimated. The type of situation which is thus excluded by this definition is one where the population is split into a number of defined areas, and separate population estimates are required for each area as well as for numbers of animals moving from one area to another. The single population, however, need not be homogeneous but may consist of different classes of animals behaving in different ways. The other assumptions underlying the model are stated with the notation in ? 2, and the generalized probability distribution is derived in ? 3.
Template Images for Nonhuman Primate Neuroimaging: 1. Baboon

Coregistration of functional brain images across many subjects offers several experimental advantages and is widely used for studies in humans. Voxel-based coregistration methods require a high-quality 3-D template image, preferably one that corresponds to a published atlas. Template images are available for human, but we could not find an appropriate template for neuroimaging studies in baboon. Here we describe the formation of a T1-weighted structural MR template image and a PET blood flow template, derived from 9 and 7 baboons, respectively. Custom software aligns individual MR images to the MRI template; human supervision is needed only to initially estimate any gross rotational misalignment. In these aligned individual images, internal subcortical fiducial points correspond closely to a photomicrographic baboon atlas with an average error of 1.53 mm. Cortical test points showed a mean error of 1.99 mm compared to the mean location for each point. Alignment of individual PET blood flow images directly to the PET template was compared to a two-step alignment process via each subject's MR image. The two transformations were identical within 0.41 mm, 0.54 degrees, and 1.0% (translation, rotation, and linear stretch; mean). These quantities provide a check on the validity of the alignment software as well as of the template images. The baboon structural MR and blood flow PET templates are available on the Internet (purl.org/net/kbmd/b2k) and can be used as targets for any image registration software.
Relative adrenal insufficiency in dogs with sepsis.

BACKGROUND A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. HYPOTHESIS That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. ANIMALS Thirty-three septic dogs admitted to a small animal intensive care unit. METHODS Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. RESULTS Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.
Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status

In utero environmental perturbations have been associated with epigenetic changes in the offspring and a lifelong susceptibility to cardiovascular diseases (CVD). DNA methylation at the ATP-binding cassette transporter A1 (ABCA1) gene was previously associated with CVD, but whether these epigenetic marks respond to changes in the maternal environment is unknown. This study was undertaken to assess the associations between the maternal metabolic profile and ABCA1 DNA methylation levels in placenta and cord blood. Placenta and cord blood samples were obtained at delivery from 100 women including 26 with impaired glucose tolerance (IGT) diagnosed following a 75 g-oral glucose tolerance test (OGTT) between week 24 and 28 of gestation. ABCA1 DNA methylation and mRNA levels were measured using bisulfite pyrosequencing and quantitative real-time PCR, respectively. We report that ABCA1 DNA methylation levels on the maternal side of the placenta are correlated with maternal high density lipoprotein cholesterol (HDL-C) levels (r < –0.21; P < 0.04) and glucose levels 2 h post-OGTT (r = 0.25; P = 0.02). On the fetal side of the placenta, ABCA1 DNA methylation levels are associated with cord blood triglyceride levels (r = –0.28; P = 0.01). ABCA1 DNA methylation variability on both sides of the placenta are also associated with ABCA1 mRNA levels (r < –0.35; P = 0.05). As opposed to placenta, cord blood DNA methylation levels are negatively correlated with maternal glucose 2 h post-OGTT (r = –0.26; P = 0.02). In conclusion, the epivariations observed in placenta and cord blood likely contribute to an optimal materno–fetal cholesterol transfer. These in utero epigenetics adaptations may also potentially trigger the long-term susceptibility of the newborn to dyslipidemia and CVD.
Cell-free DNA increase over first 48 hours in emergency intensive care unit predicts fatal outcome in patients with shock

Objective To investigate whether circulating cell-free (cf)-DNA levels are a useful biomarker for survival in patients with shock in the emergency intensive care unit (EICU). Methods This prospective observational study enrolled patients admitted to the EICU diagnosed with shock. Blood cf-DNA levels were analysed on admission, and after 24 and 48 h. As a measure of circulating cf-DNA, copy number of the β-globin gene in plasma was assessed using quantitative real-time polymerase chain reaction. Results Circulating cf-DNA levels were higher at hospital admission and after 24 h in EICU patients with shock who died than in those who recovered. Change in cf-DNA levels over the first 48 h in critical care was independently associated with 28-day mortality. The critical cut-off value for cf-DNA change over 48 h in predicting 28-day mortality was +16.12% (sensitivity 68.9%, specificity 89.7%). Conclusions Increased circulating cf-DNA levels in EICU patients with shock are associated with risk of death and measuring cf-DNA change over 48 h improves risk prediction. The present study suggests that cf-DNA may serve as a viable plasma biomarker of mortality risk in EICU patients with shock.
How to best define the metabolic syndrome

The constellation of metabolic abnormalities including centrally distributed obesity, decreased high‐density lipoprotein cholesterol (HDL‐C), elevated triglycerides, elevated blood pressure (BP), and hyperglycaemia is known as the metabolic syndrome. Associated with increased risk of both type 2 diabetes and cardiovascular disease (CVD), the metabolic syndrome is thought to be a driver of the modern day epidemics of diabetes and CVD and has become a major public health challenge around the world 1. Since its initial description, several definitions of the syndrome have emerged. Each of these definitions used differing sets of criteria, the combination of which either reflected contrasting views on pathogenic mechanisms or clinical usefulness. The use of these definitions to conduct research into the metabolic syndrome in diverse populations resulted in wide ranging prevalence rates, inconsistencies and confusion, and spurred on the vigorous debate regarding how the metabolic syndrome should be defined. In response to this controversy, the International Diabetes Federation (IDF) has recently proposed a new definition, which is applicable to populations around the world 1, 2. It is envisaged that the development of the new definition for the metabolic syndrome will help resolve the confusion caused by the number of earlier attempts to define this important entity.
Viable Intrauterine Pregnancy and Coexisting Molar Pregnancy in a Bicornuate Uterus: A Rare Presentation

A complete hydatidiform mole with a viable coexisting fetus (CMCF) is a rare occurrence. Similarly, Mullerian anomalies such as a bicornuate uterus are uncommon variants of normal anatomy. We report a case of a 40-year-old female with a known bicornuate uterus presenting at 13 weeks gestation with vaginal bleeding. Ultrasound findings showed a healthy viable pregnancy in the right horn with complete molar pregnancy in the left horn. After extensive counseling, the patient desired conservative management, however, was unable to continue due to profuse vaginal bleeding. The patient underwent suction dilation and curettage under general anesthesia and evacuation of the uterine horns. Postoperatively, the patient was followed until serum beta-human chorionic gonadotropin (β-hCG) level dropped to <5 mU. This is the first case of a CMCF reported in a bicornuate uterus, diagnosed with the use of ultrasound imaging.
Preparation and Optimization of Amorphous Ursodeoxycholic Acid Nano-suspensions by Nanoprecipitation based on Acid-base Neutralization for Enhanced Dissolution.

BACKGROUND Ursodeoxycholic acid, usually used to dissolve cholesterol gallstones in clinic, is a typical hydrophobic drug with poor oral bioavailability due to dissolution rate-limited performance. The objective of this study was to increase the dissolution of ursodeoxycholic acid by amorphous nanosuspensions. METHODS Nanoprecipitation based on acid-base neutralization was used to prepare the nanosuspensions with central composite design to optimize the formula. The nanosuspensions were characterized by particle size, morphology, crystallology and dissolution. RESULTS The ursodeoxycholic acid nanosuspensions showed mean particle size around 380 nm with polydispersion index value about 0.25. Scanning electron microscope observed high coverage of HPMC-E50 onto the surface of the nanosuspensions. Differential scanning calorimetry and powder X-ray diffractometry revealed amorphous structure of the ursodeoxycholic acid nanosuspensions. A significant increase of dissolution in acidic media was achieved by the amorphous nanosuspensions compared with the physical mixture. CONCLUSION It can be predicted that the amorphous nanosuspensions show great potential in improving the oral bioavailability of ursodeoxycholic acid.
Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation–π interactions

Alkyltransferase-like (ATL) proteins in Schizosaccharomyces pombe (Atl1) and Thermus thermophilus (TTHA1564) protect against the adverse effects of DNA alkylation damage by flagging O6-alkylguanine lesions for nucleotide excision repair (NER). We show that both ATL proteins bind with high affinity to oligodeoxyribonucleotides containing O6-alkylguanines differing in size, polarity, and charge of the alkyl group. However, Atl1 shows a greater ability than TTHA1564 to distinguish between O6-alkylguanine and guanine and in an unprecedented mechanism uses Arg69 to probe the electrostatic potential surface of O6-alkylguanine, as determined using molecular mechanics calculations. An unexpected consequence of this feature is the recognition of 2,6-diaminopurine and 2-aminopurine, as confirmed in crystal structures of respective Atl1-DNA complexes. O6-Alkylguanine and guanine discrimination is diminished for Atl1 R69A and R69F mutants, and S. pombe R69A and R69F mutants are more sensitive toward alkylating agent toxicity, revealing the key role of Arg69 in identifying O6-alkylguanines critical for NER recognition.
The thyrotropin-releasing hormone test may predict recurrence of clinical depression within ten years after discharge.

OBJECTIVES The underlying pathogenic mechanisms and predictors of recurrence in major depressive disorder are still largely unknown. Hypothalamic-pituitary-thyroid (HPT) axis and hypothalamus-pituitary-adrenocortical (HPA) axis dysregulation are thought to be related to the development and course of depression. DESIGN AND SETTING Over a ten-year period, we investigated whether the results of thyrotropin-releasing hormone (TRH) testing and combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) testing could be correlated with the recurrence of depression in 25 outpatients with clinically remitted major depression for at least 10 years. MATERIALS AND METHODS Twenty-five patients (16 women and 9 men, 48.1 years of age, SD=11.4, range 22-84) with major depressive disorder were available for evaluation during hospitalization. TRH and DEX/CRH tests were administered at admission. RESULTS Patients who recurred within ten years after remission exhibited significantly higher thyroid stimulating hormone (TSH) responses to TRH at the time of admission compared to those who did not recur. There was no significant correlation between recurrence and DEX/CRH levels after controlling for age, sex, and body mass index. CONCLUSION The findings of this study suggest that the TRH test may predict future recurrence in patients with depression.
Automatic memory management for flexible real-time systems

In a flexible real-time system, the constraints in available CPU time and memory lead to resource management problems, which must be handled carefully in order to maximize quality of service while avoiding overload. Managing CPU time -- scheduling -- is well studied and dynamic scheduling is widely accepted in the real-time industry. In order to make safe high-level languages, like Java, practically feasible for use in hard real-time systems, memory management and particularly the dependencies between memory and CPU usage must be studied. The traditional approach to incremental GC scheduling, to perform garbage collection work in proportion to the amount of allocated memory, has drawbacks such as inconsistent utilization due to bursty allocations. To remedy this, time-triggered GC scheduling is proposed. It is shown that this strategy gives real-time performance that is equal to, or better than, that of an allocation-triggered GC. It is also shown that by using a deadline-based scheduler, the GC scheduling and, consequently, the real-time performance, is independent of complex and error-prone work metrics. Time-triggered GC also allows a more high-level view on GC scheduling, as the entire GC cycle is considered rather than each individual increment. This makes it possible to schedule GC as a normal task. As the scheduling parameters are explicit in the model, it also makes the time-triggered strategy well suited for auto-tuning and fits well into feedback scheduling systems. A novel approach of applying priorities to memory allocation is introduced and it is shown how this can be used to enhance the robustness of real-time applications. The proposed mechanisms can also be used to increase performance of systems with automatic memory management by limiting the amount of garbage collection work. Together, these solutions facilitate flexible and robust automatic memory management for real-time systems. Adaptive techniques are presented, aimed at replacing or complementing a priori analysis with on-line auto-tuning. The presented ideas have been successfully implemented and validated in an experimental real-time Java environment, supporting the claim that this work is a step towards write once -- run anywhere with hard real-time performance.
Graph decomposition: A new key to coding theorems

A new and simple method is proposed for finding good encoders both for channels and for sources with side information. This method relies on the continuous version of a graph decomposition result of Lovasz. The presently known best exponential error bounds for both problems follow in a unified manner with an improvement on the source coding bound. The previous bounds for universal codes of the authors and Marton are also improved.
Aging Resistance Properties of Poplar Plywood Bonded by Soy Protein-Based Adhesive

The aging resistance properties of poplar plywood prepared with soy protein-based adhesives were investigated. The shear strength of soybean meal/bisphenol epoxy resin (SM/EP) adhesive increased by 197.5% (surface layer) to 1.19 MPa and 153.5% (core layer) to 1.09 MPa compared to soybean meal (SM) adhesive. Wet-dry cycles of 25 ± 3 °C, 63 ± 2 °C, and 95 ± 2 °C accelerated the aging of poplar plywood with soy protein-based adhesive. After eight 25 ± 3 °C wet-dry cycles, the shear strength of plywood bonded with SM/EP adhesive was reduced to 0.88 MPa (surface layer) and 0.71 MPa (core layer). Furthermore, the shear strength of SM adhesive gradually decreased to 0 (surface and core layer) after six and five 25 ± 3 °C wet-dry cycles. The shear strength of SM/EP adhesives was reduced to 0.96 MPa and 0.79 MPa (surface and core layer) after eight 63 ± 2 °C wet-dry cycles, and 0.53 MPa and 0.27 MPa (surface and core layer) after eight 95 ± 2 °C wet-dry cycles. Vertical density profiles indicated that the decrease of shear strength could be attributed to several factors: The small molecules were dissolved, the molecular chains of the adhesives were hydrolyzed by water, and the interior and thermal stress destroyed the bonding structure.