Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenovirus E3 protein causes constitutively internalized epidermal growth factor receptors to accumulate in a prelysosomal compartment, resulting in enhanced degradation

We have previously identified and characterized an integral membrane protein coded for by the early transcription region 3 (E3) of human group C adenoviruses that down-regulates the epidermal growth factor receptor (EGFR). The goal of this study was to characterize the early receptor trafficking events leading to enhanced EGFR degradation in adenovirus-infected cells. Specifically, we wished to determine whether adenovirus increases the rate of EGFR internalization or alters the subcellular compartmentalization of internalized EGFRs. Once the optimal time for measuring early trafficking events was determined, surface EGFRs were labeled with a cleavable biotin reagent to measure internalization rates and with a receptor-specific monoclonal antibody (MAb) conjugated to colloidal gold for intracellular localization studies. We first showed that the rate of EGFR internalization in adenovirus-infected cells is indistinguishable from the constitutive internalization rate for unoccupied EGFRs. The possibility that the E3 protein can affect trafficking of EGFRs internalized at a low constitutive rate was further supported by studies showing that adenovirus-mediated down-regulation occurs independently of EGFR oligomerization and intrinsic EGFR tyrosine kinase activity, which are required for efficient ligand-induced internalization. Other tyrosine kinases inhibited by genistein are also not required for adenovirus-induced down-regulation. When the intracellular localization of EGFRs during adenovirus-mediated down-regulation was examined by electron microscopy, there was a threefold increase in the number of EGFRs localized to multivesicular bodies. The multivesicular body has been proposed to be important for regulating intracellular membrane protein sorting, since trafficking patterns for receptors that recycle and receptors that are degraded diverge in this organelle. These data therefore suggest that adenovirus may enhance EGFR degradation by causing constitutively internalized EGFRs to accumulate in a prelysosomal compartment. This is the first example of a mechanism that efficiently down-regulates EGFR without significantly increasing the rate of internalization or that does not require EGFR tyrosine kinase activity. Since viral proteins often mimic or modify a host counterpart, this suggests that there are normal physiological conditions when receptor destruction without tyrosine signalling is beneficial.
Notes on food, beverages and fomites contaminated with Vibrio cholerae.

The survival of cholera vibrios outside the human body has been studied by numerous authors.a -c However, the strains and the techniques used in these studies have varied so greatly that their results are not comparable. The intention of the present communication is to call attention to a method that is feasible for the studies of the survival time of vibrios on and in food, beverages and fomites and which attempts to approach strictly " natural " conditions. This method was developed during earlier investigations of the survival of salmonellae and shigellae on food.d When it became evident that the cholera epidemic in Thailand in 1958-60 was accompanied by a widespread contamination of food and water with cholera vibrios,e, f it became necessary to re-evaluate the relationship of Vibrio cholerae to food and water. The relatively long survival of El Tor organisms outside the human body and the role of sea-food in cholera infections had been noted.c At the same time, a systematic investigation of the survival time of freshly isolated cholera vibrios in and on vegetables, fruits, meats and dishes commonly consumed by Thais and by occidentals living in Thailand was initiated, keeping the two following problems in sight. One of these problems was the duration of survival of cholera vibrios on food shipped in international and in intra-state commerce. It was deemed advisable to determine which of such food-stuffs might serve as vehicles for the transmission of cholera from one locality to another. Since such food shipments may
Absorption of Volatile Organic Compounds into Polydimethylsiloxane: Phase Equilibrium Computation at Infinite Dilution

Group contribution methods such as the UNIFAC are very useful to researchers and engineers involved in synthesis, feasibility studies, design and optimization of separation processes. They can be applied successfully to predict phase equilibrium and excess properties in the development of chemical and separation processes. The main focus of this work was to investigate the possibility of absorbing selected volatile organic compounds (VOCs) into polydimethylsiloxane (PDMS) using three selected UNIFAC group contribution methods. Absorption followed by subsequent stripping is the predominant available abatement technology of VOCs from flue gases prior to their release into the atmosphere. The original, modified and effective UNIFAC models were used in this work. The thirteen selected VOCs that have been considered in this research are: pentane, hexane, heptanes, trimethylamine, toluene, xylene, cyclohexane, butyl acetate, diethyl acetate, chloroform, acetone, ethyl methyl ketone and isobutyl methyl ketone. The computation was done for solute VOC concentration of 8.55x10 -8 which is well in the infinite dilution region. The results obtained in this study compare very well with those published in literature obtained through both measurements and predictions. The phase equilibrium obtained in this study show that PDMS is a good absorbent for the removal of VOCs from contaminated air streams through physical absorption.
Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise

We determined whether mitogen‐activated protein kinase (MAPK) and 5′‐AMP‐activated protein kinase (AMPK) signalling cascades are activated in response to intense exercise in skeletal muscle from six highly trained cyclists (peak O2 uptake (V̇O2,peak) 5.14 ± 0.1 l min−1) and four control subjects (V̇O2,peak 3.8 ± 0.1 l min−1) matched for age and body mass. Trained subjects completed eight 5 min bouts of cycling at ≈85% of V̇O2,peak with 60 s recovery between work bouts. Control subjects performed four 5 min work bouts commencing at the same relative, but a lower absolute intensity, with a comparable rest interval. Vastus lateralis muscle biopsies were taken at rest and immediately after exercise. Extracellular regulated kinase (ERK1/2), p38 MAPK, histone H3, AMPK and acetyl CoA‐carboxylase (ACC) phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activity of mitogen and stress‐activated kinase 1 (MSK1; a substrate of ERK1/2 and p38 MAPK) and α1 and α2 subunits of AMPK were determined by immune complex assay. ERK1/2 and p38 MAPK phosphorylation and MSK1 activity increased (P < 0.05) after exercise 2.6‐, 2.1‐ and 2.0‐fold, respectively, in control subjects and 1.5‐, 1.6‐ and 1.4‐fold, respectively, in trained subjects. Phosphorylation of histone H3, a substrate of MSK1, increased (P < 0.05) ≈1.8‐fold in both control and trained subject. AMPKα2 activity increased (P < 0.05) after exercise 4.2‐ and 2.3‐fold in control and trained subjects, respectively, whereas AMPKα1 activity was not altered. Exercise increased ACC phosphorylation (P < 0.05) 1.9‐ and 2.8‐fold in control and trained subjects. In conclusion, intense cycling exercise in subjects with a prolonged history of endurance training increases MAPK signalling to the downstream targets MSK1 and histone H3 and isoform‐specific AMPK signalling to ACC. Importantly, exercise‐induced signalling responses were greater in untrained men, even at the same relative exercise intensity, suggesting muscle from previously well‐trained individuals requires a greater stimulus to activate signal transduction via these pathways.
Noise‐rearing disrupts the maturation of multisensory integration

It is commonly believed that the ability to integrate information from different senses develops according to associative learning principles as neurons acquire experience with co‐active cross‐modal inputs. However, previous studies have not distinguished between requirements for co‐activation versus co‐variation. To determine whether cross‐modal co‐activation is sufficient for this purpose in visual–auditory superior colliculus (SC) neurons, animals were reared in constant omnidirectional noise. By masking most spatiotemporally discrete auditory experiences, the noise created a sensory landscape that decoupled stimulus co‐activation and co‐variance. Although a near‐normal complement of visual–auditory SC neurons developed, the vast majority could not engage in multisensory integration, revealing that visual–auditory co‐activation was insufficient for this purpose. That experience with co‐varying stimuli is required for multisensory maturation is consistent with the role of the SC in detecting and locating biologically significant events, but it also seems likely that this is a general requirement for multisensory maturation throughout the brain.
Supersaturation and crystallization: non-equilibrium dynamics of amorphous solid dispersions for oral drug delivery

ABSTRACT Introduction: Amorphous solid dispersions (ASDs) are one of the key formulation technologies that aid the development of poorly soluble candidates. However, their dynamic behaviors, including dissolution and crystallization processes, are still full of mystery. Further understanding of these processes should enhance their wider use. Areas covered: The first part of this review describes the current understanding of the dissolution of ASDs, where phase separation behavior is frequently involved and attempts to develop appropriate dissolution tests to achieve an in vitro–in vivo correlation are examined. The second part of this review discusses crystallization of the drug molecule with the eventual aim of establishing an accelerated testing protocol for predicting its physical stability. Expert opinion: The phase separation behavior from the supersaturated state during the dissolution test must be understood, and its relevance to the oral absorption behavior needs to be clarified. Research efforts should focus on the differences between the phase behavior in in vitro and in vivo situations. Initiation time of the crystallization was shown to be predicted only from storage and glass transition temperatures. This finding should encourage the establishment of testing protocol of the physical stability of ASDs.
Comparison of older adult subject and proxy responses on the SF-36 health-related quality of life instrument

Abstract Studies of older adults' health status and health-related quality of life (HRQoL) often rely on proxy responses when subjects have problems that affect their ability to respond. With the increased interest in outcomes research in health care, it is important to examine proxy reliability on HRQoL instruments. This study compares 32 pairs of subject-and-proxy responses on the eight subscales and two summary scales of the Short Form 36 (SF-36). Subjects and their proxies, recruited from senior centers and residential facilities, were interviewed face-to-face within a seven-day period. Subjects were 60 years of age or older and had passed a brief cognitive screen, and proxies were geographically proximate and had seen the subject during the past week. Results showed that although moderate intra-class correlations were found on six of the eight measures, an item-level kappa statistic indicated poor to fair agreement on all subscales except items of Physical Functioning and Role Physical. Moreover, paired t-tests revealed proxy mean scores that were significantly lower on the Physical Functioning, Vitality, and Mental Health subscales. Given the mixed findings, until further research is done, researchers and clinicians should exercise caution when using proxy responses for older adults with the SF-36.
An immunogen synthesis strategy for the development of specific anti-deoxynivalenol monoclonal antibodies

An immunogen synthesis strategy was designed to develop anti-deoxynivalenol (DON) monoclonal antibodies with low cross-reactivity against structurally similar trichothecenes. A total of eight different DON immunogens were synthesised, differing in the type and position of the linker on the DON molecule. After immunisation, antisera from mice immunised with different DON immunogens were checked for the presence of relevant antibodies. Then, both homologous and heterologous enzyme-linked immunosorbent assays (ELISAs) were performed for hybridoma screening. Finally, three monoclonal antibodies against DON and its analogues were generated. In addition, monoclonal antibody 13H1 could recognise DON and its analogues in the order of HT-2 toxin > 15-acetyldeoxynivalenol (15-ADON) > DON, with IC50 ranging from 1.14 to 2.13 µg ml–1. Another monoclonal antibody 10H10 manifested relatively close sensitivities to DON, 3-acetyldeoxynivalenol (3-ADON) and 15-ADON, with IC50 values of 22, 15 and 34 ng ml–1, respectively. Using an indirect ELISA format decreases the 10H10 sensitivity to 15-ADON with 92%. A third monoclonal antibody 2A9 showed to be very specific and sensitive to 3-ADON, with IC50 of 0.38 ng ml–1. Using both 2A9 and 10H10 monoclonal antibodies allows determining sole DON contamination.
Cryptographically secure detection of mirror worlds

The Resource Public Key Infrastructure (RPKI) has been introduced as a way of authorizing Border Gateway Protocol (BGP) route announcements. The highly centralized structure of the RPKI provides security guarantees against external threats, e.g. prefix hijacking, but allows for the unilateral revocation of allocated resources. Recent efforts propose changes to the RPKI to create accountability of such unilateral actions. The project under consideration continues these efforts by providing a mechanism for ensuring global consistency. We solve the global consistency problem by constructing a k–connected graph containing all 2–party audits that the honest Autonomous Systems must perform to ensure that no mirror worlds exist.
Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing

There are now more than 5 experimental vaccine formulations which induce T and B cell immunity towards the internally situated virus proteins matrix (M1 and M2e) and nucleoprotein (NP), and towards stem and stalk regions of the HA which have a shared antigenic structure amongst many of the 17 influenza A virus sub types. Such ‘universal vaccines’ could be used, at least in theory, as a prophylactic stockpile vaccine for newly emerged epidemic and novel pandemic influenza A viruses or as a supplement to conventional HA/NA vaccines. My own laboratory has approached the problem from the clinical viewpoint by identifying CD4+ cells which are present in influenza infected volunteers who resist influenza infection. We have established precisely which peptides in M and NP proteins react with these immune CD4 cells. These experimental vaccines induce immunity in animal models but with a single exception no data have been published on protection against influenza virus infection in humans. The efficacy of the latter vaccine is based on vaccinia virus (MVA) as a carrier and was analyzed in a quarantine unit. Given the absence of induced HI antibody in the new universal vaccines a possible licensing strategy is a virus challenge model in quarantine whereby healthy volunteers can be immunized with the new vaccine and thereafter deliberately infected and clinical signs recorded alongside quantities of virus excreted and compared with unvaccinated controls.
Ad libitum fluid replacement in military personnel during a 4-h route march.

INTRODUCTION Opportunities to determine optimal rates of fluid ingestion could reduce the mass soldiers might need to carry on military missions. PURPOSE The first objective was to evaluate the effects of an ad libitum fluid replacement strategy on total body water (TBW), core temperature, serum sodium concentrations [Na+], and plasma osmolality (POsm). The second objective was to determine if an ad libitum water intake was sufficient to maintain these variables during exercise. A third objective was to determine if changes in body mass are an accurate measure of changes in TBW. METHODS A field study was conducted with 15 soldiers performing a 16.4-km route march. The average age of 15 subjects was 27 yr (SD = 4.6 yr). RESULTS Their mean hourly ad libitum fluid intake was 383 mL (SD = 150 mL). Predicted sweat rate was 626 +/-122 mL.h-1. Despite an average body mass loss of 1.0 kg (SD = 0.50 kg) TBW, POsm and serum [Na+] did not change significantly during exercise. There was a significant (P < 0.05) linear relationship with a negative slope between postexercise serum [Na+] and changes in both body mass and percentage of TBW. Postexercise POsm and serum [Na+] were significantly related (P < 0.05). Higher postexercise percentage of TBW was associated with lower postexercise POsm and serum [Na+] levels. There was no relation between percent body mass loss and postexercise core temperature (38.1 degrees C +/- 0.6 degrees C). CONCLUSIONS A mean ad libitum water intake of 383 mL.h-1, replacing approximately 61% of body mass losses during 4 h of exercise, maintained TBW, core temperature, POsm, and serum [Na+] despite a 1.4% body mass loss. A reduction in body mass of 1.4% (1.0 kg) was not associated with a reduction in TBW.
Hamiltonian inclusive fitness: a fitter fitness concept

In 1963–1964 W. D. Hamilton introduced the concept of inclusive fitness, the only significant elaboration of Darwinian fitness since the nineteenth century. I discuss the origin of the modern fitness concept, providing context for Hamilton's discovery of inclusive fitness in relation to the puzzle of altruism. While fitness conceptually originates with Darwin, the term itself stems from Spencer and crystallized quantitatively in the early twentieth century. Hamiltonian inclusive fitness, with Price's reformulation, provided the solution to Darwin's ‘special difficulty’—the evolution of caste polymorphism and sterility in social insects. Hamilton further explored the roles of inclusive fitness and reciprocation to tackle Darwin's other difficulty, the evolution of human altruism. The heuristically powerful inclusive fitness concept ramified over the past 50 years: the number and diversity of ‘offspring ideas’ that it has engendered render it a fitter fitness concept, one that Darwin would have appreciated.
Finding subject terms for classificatory metadata from user-generated social tags

With the increasing popularity of social tagging systems, the potential for using social tags as a source of metadata is being explored. Social tagging systems can simplify the involvement of a large number of users and improve the metadata‐generation process. Current research is exploring social tagging systems as a mechanism to allow nonprofessional catalogers to participate in metadata generation. Because social tags are not from controlled vocabularies, there are issues that have to be addressed in finding quality terms to represent the content of a resource. This research explores ways to obtain a set of tags representing the resource from the tags provided by users. Two metrics are introduced. Annotation Dominance (AD) is a measure of the extent to which a tag term is agreed to by users. Cross Resources Annotation Discrimination (CRAD) is a measure of a tag's potential to classify a collection. It is designed to remove tags that are used too broadly or narrowly. Using the proposed measurements, the research selects important tags (meta‐terms) and removes meaningless ones (tag noise) from the tags provided by users. To evaluate the proposed approach to find classificatory metadata candidates, we rely on expert users' relevance judgments comparing suggested tag terms and expert metadata terms. The results suggest that processing of user tags using the two measurements successfully identifies the terms that represent the topic categories of web resource content. The suggested tag terms can be further examined in various usages as semantic metadata for the resources.
Architectural Design Decision Documentation through Reuse of Design Patterns

While design decisions on the application of architectural design patterns involve complex trade-offs between functionality and quality properties, such decisions are often spontaneous, and documentation of decisions and trace links to related artefacts is usually insufficient. The approach proposed in this thesis provides a support to overcome these problems. It combines support for evaluation of design pattern application, and semi-automated documentation of decisions and trace links.
Profiling of autoantibodies in IgA nephropathy, an integrative antibiomics approach.

BACKGROUND AND OBJECTIVES IgG commonly co-exists with IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) with unclear clinical relevance. Autoantibody (autoAb) biomarkers to detect and track progression of IgAN are an unmet clinical need. The objective of the study was to identify IgA-specific autoAbs specific to IgAN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS High-density protein microarrays were evaluated IgG autoAbs in the serum of IgAN patients (n = 22) and controls (n = 10). Clinical parameters, including annual GFR and urine protein measurements, were collected on all patients over 5 years. Bioinformatic data analysis was performed to select targets for further validation by immunohistochemistry (IHC). RESULTS One hundred seventeen (1.4%) specific antibodies were increased in IgAN. Among the most significant were the autoAb to the Ig family of proteins. IgAN-specific autoAbs (approximately 50%) were mounted against proteins predominantly expressed in glomeruli and tubules, and selected candidates were verified by IHC. Receiver operating characteristic analysis of our study demonstrated that IgG autoAb levels (matriline 2, ubiquitin-conjugating enzyme E2W, DEAD box protein, and protein kinase D1) might be used in combination with 24-hour proteinuria to improve prediction of the progression of IgAN (area under the curve = 0.86, P = 0.02). CONCLUSIONS IgAN is associated with elevated IgG autoAbs to multiple proteins in the kidney. This first analysis of the repertoire of autoAbs in IgAN identifies novel, immunogenic protein targets that are highly expressed in the kidney glomerulus and tubules that may bear relevance in the pathogenesis and progression of IgAN.
X-band TR module for radar and wireless communication systems

The paper presents the design and fabrication of an X-band transmit receive module operating in the frequency range of 9.25 to 10.75 GHz. The proposed TR module consists of a circulator, a power amplifier and a low-noise amplifier, which are fabricated using hybrid microwave integrated circuit technology. Amplifier design procedures are presented with focuses on stability improvement, wideband matching and noise matching techniques to improve amplifiers' performances. The designed power amplifier with good input and output matching exhibits 15-dB power gain and provides measured output power of 15.1 dBm and OP1dB of 22.5 dBm. The designed low noise amplifier has a very low measured noise figure of 2 dB and a high gain of 20 dB over the whole bandwidth, good input/output matching is also achieved with measured S11 and S22 smaller than -10 and -12 dB, respectively. Amplifiers are integrated with circulator to build a complete TR module which helps extend operating range of radar and wireless communication systems.