Miracle-dz/UniFAR-FTUs huggingface dataset:
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen

PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and stability toward proteases, however their size lowers to some extent their potential because of a reduced ability to penetrate tissues, especially those of tumor origin. Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much less well retained in circulation. We have here investigated the effects of various PEGylations on the binding properties and in vivo half-life of Fab fragments derived from the enzymatic splitting of Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects the ability to recognize the target antigen in a way that is dependent on the extent and position of the chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must be carefully considered for the design of strategies based on the use of antibody fragments.
Ruthenium Carbene Mediated Metathesis of Oleate-Type Fatty Compounds

The complexes RuCl2(PCy3)2(=CHPh), 1, and RuCl2(PCy3)(H2IMes)(=CHPh), 2, proved to be active catalysts for the self-metathesis of oleate-type fatty compounds containing the ester, hydroxyl, epoxy and carboxylic acid functional groups. At elevated reaction temperatures 2 showed a higher activity, stability and lower selectivity for primary metathesis products compared to 1. A profound influence of organic functional groups on catalyst activity and selectivity was found and from relative activities and selectivities 2 has proved to be more resistant to deactivation by polar functional groups and more inclined to promote double bond isomerisation than 1. The observed catalyst deactivation by oxygen-containing functional groups could be attributed to a phosphine displacement side reaction.
Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa

Infection with HIV, and oftentimes coinfection with TB, complicates the care of severely malnourished children in sub-Saharan Africa. These superimposed infections challenge clinicians faced with a population of malnourished children for whose care evidence-based guidelines have not kept up. Even as the care of HIV-uninfected malnourished children has improved dramatically with the advent of community-based care and even as there are hopeful signs that the HIV epidemic may be stabilizing or ameliorating, significant gaps remain in the care of malnourished children with HIV. Here we summarize what is currently known, what remains unknown, and what remains challenging about how to treat severely malnourished children with HIV and TB.
Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients

The open-label, phase II clinical trial of antituberculosis therapy (ATT) with or without oral immunomodulator Dzherelo (Immunoxel) was conducted in TB/HIV coinfected, antiretroviral therapy naïve patients to evaluate the effect on CD4 T-lymphocyte counts and viral load. The arm A (n = 20) received isoniazid (H); rimfapicin (R); pyrazinamide (Z); streptomycin (S); and ethambutol (E), and arm B (n = 20) received 50 drops of Dzherelo twice per day in addition to HRZSE. After 2 months in 90% of Dzherelo patients the population of absolute CD4 T-cells expanded by an average of 71.2% (from 174 to 283 cells/μl; P = 0.00003), but declined in ATT-alone patients (182 to 174; P = 0.34). The ratio between CD4/CD8 cells deteriorated in 80% of individuals in arm A (1.213 > 0.943; P = 0.002), but improved in the same proportion of patients in arm B (1.244 > 1.536; P = 0.007). The number of total CD3+ lymphocytes rose from 728 to 921 cells in arm B (P = 0.025) whereas it fell from 650 to 585 cells in arm A (P = 0.25). The viral load, as measured by plasma RNA-PCR, decreased in 70% of Dzherelo recipients (2.174 > 1.558 copies/ml; P = 0.002), but increased in 70% of HRZSE only receivers (1.907 > 2.076 copies/ml; P = 0.03). Dzherelo has a favorable effect on the immune status and viral burden in TB/HIV patients when given as an immunomodulating adjunct to ATT.
Gaming to see: action video gaming is associated with enhanced processing of masked stimuli

Recent research revealed that action video game players outperform non-players in a wide range of attentional, perceptual and cognitive tasks. Here we tested if expertise in action video games is related to differences regarding the potential of shortly presented stimuli to bias behavior. In a response priming paradigm, participants classified four animal pictures functioning as targets as being smaller or larger than a reference frame. Before each target, one of the same four animal pictures was presented as a masked prime to influence participants' responses in a congruent or incongruent way. Masked primes induced congruence effects, that is, faster responses for congruent compared to incongruent conditions, indicating processing of hardly visible primes. Results also suggested that action video game players showed a larger congruence effect than non-players for 20 ms primes, whereas there was no group difference for 60 ms primes. In addition, there was a tendency for action video game players to detect masked primes for some prime durations better than non-players. Thus, action video game expertise may be accompanied by faster and more efficient processing of shortly presented visual stimuli.
CENTRAL CONTROL OF AN INSECT

A previous paper (McKay, 1969) described the response characteristics of the large auditory T fibre of the tettigoniid Homorocoryphus. This neurone is both frequencysensitive and amplitude-sensitive, and does not respond to the species song. It responds preferentially to short, high-frequency sounds, which, together with the large size of the axon, suggests that it may function as a warning neurone. Recent work by Rowell & McKay (1969) indicates that the responsiveness of insect sensory interneurones can be controlled by auxilliary inputs, often inhibitory, which are central in origin. Rowell (1964) found that lesions in the central nervous system of Schistocerca increased the frequency of a behavioural reflex controlled by the prothoracic ganglion. Increased responsiveness was correlated with a decrease in the input to the ganglion, and increased output from it (Rowell, 1969), indicating that inhibitory influences had been interrupted by the lesions. Rowell & McKay (1969) found that disconnecting the head ganglia of Gastrimargus from the rest of the central nervous system markedly increased the responsiveness of the alpha auditory interneurone, while subsequent lesions had little or no effect. Habituation is also controlled by central factors. Habituation is the waning of a response to a repeated stimulus, and is seen in many vertebrate sensory interneurones (Horn, in press) and in a growing number of invertebrate sensory interneurones (Horridge, Scholes, Shaw & Tunstall 1965; Horn & Rowell, 1968, Rowell & McKay, 1969). Habituation is characterized by stimulus specificity, recovery after a time lapse, and sometimes by dishabituation by another modality of stimulus (Horn, 1967). It is an important property of interneurones in that it enables repetitive, irrelevant stimuli to be ignored, and novel stimuli to be recognized easily. Visual units in the tritocerebrum and ventral nerve of Schistocerca (Horn & Rowell, 1968; Rowell & Horn, 1968; Palka, 1967) show complex habituation phenomena which may last for several hours. Similar characteristics have been observed in the alpha auditory interneurone of Gastrimargus (Rowell & McKay, 1969). The habituation rate of this interneurone is decreased by the removal of the head ganglia, but other lesions to the central nervous system have very little effect. This paper describes the effect of lesions to the central nervous system on the responsiveness and habituation rate of the large auditory T fibre of the tettigoniid, Homorocoryphus. The results suggest that the response level of the interneurone is controlled by an inhibitory input or inputs, which originate within the posterior
Coherent vortex simulation of three-dimensional turbulent mixing layers using orthogonal wavelets

This paper assesses the potential of coherent vortex simulation (CVS) to compute three-dimensional turbulent mixing layers. CVS splits each turbulent flow realization into two orthogonal parts, one corresponding to coherent vortices which are kept, and the other to an incoherent background flow which is discarded. The CVS filter is applied to data from direct numerical simulations (DNS) of three-dimensional forced and unforced time-developing turbulent mixing layers. The coherent flow is represented by few wavelet modes, but these are sufficient to reproduce the vorticity probability distribution function and the energy spectrum out to the high-wavenumber end of the inertial range. The discarded incoherent background flow is homogeneous, small-amplitude and decorrelated. The CVS-filtering results are then compared with those obtained for the same compression ratio using Fourier low-pass filtering, as employed in large-eddy simulation (LES). Compared to the incoherent background flow of CVS filtering, the subgrid scales of LES filtering are less homogeneous, have much larger amplitude, and exhibit spatial correlations that makes modelling them a difficult challenge. Finally we present simulations of a time-developing mixing layer where the CVS filter is applied at each time step. The results show that CVS preserves the nonlinear dynamics of the flow, and that discarding the incoherent modes is sufficient to model turbulent dissipation.
Integral Sliding Mode Control for Nonlinear Systems With Matched and Unmatched Perturbations

We consider the problem of designing an integral sliding mode controller to reduce the disturbance terms that act on nonlinear systems with state-dependent drift and input matrix. The general case of both, matched and unmatched disturbances affecting the system is addressed. It is proved that the definition of a suitable sliding manifold and the generation of sliding modes upon it guarantees the minimization of the effect of the disturbance terms, which takes place when the matched disturbances are completely rejected and the unmatched ones are not amplified. A simulation of the proposed technique, applied to a dynamically feedback linearized unicycle, illustrates its effectiveness, even in presence of nonholonomic constraints.
Cervical and serum IgA and serum IgG antibodies to Chlamydia trachomatis and herpes simplex virus in threatened abortion: a prospective study

Summary. The aetiological role of Chlamydia trachomatis (CT) and herpes simplex virus (HSV) was investigated in 189 patients with threatened abortion. Assessment of infection was based on isolation, and on determination of serum immunoglobulin (Ig)G and IgA antibodies as well as cervical IgA antibody levels with new sensitive radioimmunoassay (RIA) techniques. One third of the women were delivered of a healthy infant and two thirds aborted, but the two groups were otherwise clinically similar. By isolation, only 2.7% of the patients were CT‐positive, but increased cervical IgA antibody level to CT was detected in 41.3%. The mean level of these local antibodies was similar in both study groups, but the mean levels of serum IgA and IgG antibodies were somewhat higher in the patients who aborted although the difference was not significant. None of the cervical specimens was positive for HSV by isolation but the cervical IgA antibody level to HSV was raised in 47.1% of the patients. Both cervical and serum IgA antibody levels to HSV were significantly raised among the patients who aborted, but there were no differences between the patients with spontaneous abortion and those with a blighted ovum. There was no clear association between CT and abortion, but an association between HSV and abortion is possible. The incidence of raised levels of both CT and HSV IgA antibodies in the cervix was surprisingly high in both groups and the significance of this finding remains to be investigated.
Game Theory Analysis of the Bribery Behavior

Bribery may destroy the social welfare. In this paper, we investigated the mechanism of the bribery behavior based on the non-cooperative static game theory. With the general presumption of “rational player”, two bimatrix game models are established to analyze the strategy choice of the briber and the bribee. After discussing the cost-benefit of the players, some beneficial conclusions and solving measures are drawn out.
Quantification of adenovirus species B and C viremia by real‐time PCR in adults and children undergoing stem cell transplantation

Adenovirus infection during stem cell transplantation is associated with high morbidity and mortality. Adenovirus species B and C have been the main causes for these infections; however, epidemiological details about the species are still unclear. To clarify the contributions of species B and C adenovirus, the DNA was tested serially by quantitative real‐time PCR in peripheral blood, stool and urine of 32 patients (16 adults and 16 children) undergoing stem cell transplantation. Adenovirus species B viremia was detected in 10 of 16 adult and 6 of 16 pediatric transplant recipients. Adenovirus species C viremia was also detected simultaneously in five adult and three pediatric recipients. The stool and urine of patients with adenovirus viremia were also positive for the same adenovirus species as in blood. In contrast, in none of 50 healthy adult controls was adenovirus species B or C viremia detected. Among patients who developed adenovirus viremia, one adult recipient developed disseminated disease and died from multiple organ failure. The remaining patients experienced fever of several degrees and/or diarrhea during the period of adenovirus viremia; however, they all recovered without antiviral therapy. The results indicated that stem cell transplantation was frequently associated with adenovirus species B or C viremia, although it did not always cause serious infectious complications. J. Med. Virol. 79:278–284, 2007. © 2007 Wiley‐Liss, Inc.
Tension and Torsion Properties of Some Metals under Repeated Dynamic Loading (Impact)

Two new machines for the testing of metals to fracture under repeated dynamic loading in both tension and torsion are described. These machines are of the ‘falling weight’ type, the yield stress (or yield torque) being measured electronically and the total extension (or total twist) during a particular loading cycle being limited to any desired value.A preliminary series of tests in both dynamic tension and dynamic torsion, using solid cylindrical bar specimens of 3/8 inch diameter, was carried out on a medium-carbon steel, a mild steel, a silico-manganese spring steel, and two aluminium alloys. For tension, the average time from zero stress to the dynamic yield stress was in the range 0·18-1·00 milliseconds and, for torsion, 0·65-2·67 milliseconds from zero torque to the dynamic yield torque.In straining specimens to fracture under such repeated dynamic loading, the yield point was found to vary in a manner similar to that for static loading, though all dynamic yield points showed a progressive increase .
Crosslinked poly(vinyl alcohol) and starch composite films. II. Physicomechanical, thermal properties and swelling studies

Poly(vinyl alcohol) (PVA) was blended with 10, 20, 30, 40, and 50 wt % of starch with and without crosslinking by solution casting process. The solution-casted films were dried and tested for physicomechanical properties like tensile strength, tensile elongation, tensile modulus, tear and burst strengths, density, and thermal analysis by differential scanning calorimetry (DSC). These PVA/starch films were further characterized for moisture content; solubility resistance in water, 5% acetic acid, 50% ethanol, and sunflower oil; and swelling characteristics in 50% ethanol and sunflower oil. The crosslinked PVA/starch composite films show significant improvement in tensile strength, tensile modulus, tear and burst strengths, and solubility resistance over the uncrosslinked films. Between the crosslinked and uncrosslinked films, the uncrosslinked films have higher tensile elongation, moisture content, moisture absorption, and swelling over the crosslinked films. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 909–916, 2007
How to attribute causality in quality improvement: lessons from epidemiology

Quality improvement and implementation (QI&I) initiatives face critical challenges in an era of evidence-based, value-driven patient care. Whether front-line staff, large organisations or government bodies design and run QI&I, there is increasing need to demonstrate impact to justify investment of time and resources in implementing and scaling up an intervention. Decisions about sustaining, scaling up and spreading an initiative can be informed by evidence of causation and the estimated attributable effect of an intervention on observed outcomes. Achieving this in healthcare can be challenging, where interventions often are multimodal and applied in complex systems.1 Where there is weak evidence of causation, credibility in the effectiveness of the intervention is reduced with a resultant reduced desire to replicate. The greater confidence of a causal relationship between QI&I interventions and observed results, the greater our confidence that improvement will result when the intervention occurs in different settings. Guidance exists for design, conduct, evaluation and reporting of QII2–4; the Standards for QUality Improvement Reporting Excellence (SQUIRE) and the Standards for Reporting Implementation Studies (STARI) guidelines were developed specifically for reporting QI&I initiatives.5 6 However, much of this guidance is targeted at larger formal evaluations, and may require levels of resource or expertise not available to all QI&I initiatives. This paper proposes QI&I initiatives, regardless of scope and resources, can be enhanced by applying epidemiological principles, adapted from those promulgated by Austin Bradford Hill.7 Hill proposed nine ‘aspects of association’ that could be considered before ‘… deciding that the most likely interpretation is causation ’. 7 His objective was to improve the ability to form scientific judgements about causality. The nine aspects, subsequently referred to as the ‘Bradford Hill Criteria’ (BHC), are considered in the following sections. With roots in causes of disease, the BHC have natural alignment with healthcare. …
Miltefosine in the treatment of leishmaniasis: Clinical evidence for informed clinical risk management

Visceral leishmaniasis (VL) is a life-threatening disease. Traditional treatment with pentavalent antimony injections has become ineffective in the area with the world’s highest prevalence of disease (North Bihar, India) and is becoming less effective elsewhere as well. A replacement is needed, best if it can be given to more patients outside the hospital. Miltefosine is the first oral drug registered for VL. Given daily under medical supervision for 4 weeks, it cures 94% of patients (both children and adults) and is reasonably safe. Miltefosine has great potential for improving access to treatment and overall control of VL and will be critical in the VL elimination campaign in the Indian subcontinent, but must be safeguarded or will be lost if misused. Its main limitations are adherence (and hence potential for selection of drug resistant parasites) and teratogenicity (pregnancy must be avoided during treatment and the following two months). This calls for responsible deployment, setting in place mechanisms to protect female patients in child-bearing age, monitoring effects and optimizing adherence in real-life conditions through directly observed therapy. One option to protect the useful life-span of miltefosine consists in shortening treatment duration by combining it with another drug.
Toward literature-based feature selection for diagnostic classification: a meta-analysis of resting-state fMRI in depression

Information derived from functional magnetic resonance imaging (fMRI) during wakeful rest has been introduced as a candidate diagnostic biomarker in unipolar major depressive disorder (MDD). Multiple reports of resting state fMRI in MDD describe group effects. Such prior knowledge can be adopted to pre-select potentially discriminating features for diagnostic classification models with the aim to improve diagnostic accuracy. Purpose of this analysis was to consolidate spatial information about alterations of spontaneous brain activity in MDD, primarily to serve as feature selection for multivariate pattern analysis techniques (MVPA). Thirty two studies were included in final analyses. Coordinates extracted from the original reports were assigned to two categories based on directionality of findings. Meta-analyses were calculated using the non-additive activation likelihood estimation approach with coordinates organized by subject group to account for non-independent samples. Converging evidence revealed a distributed pattern of brain regions with increased or decreased spontaneous activity in MDD. The most distinct finding was hyperactivity/hyperconnectivity presumably reflecting the interaction of cortical midline structures (posterior default mode network components including the precuneus and neighboring posterior cingulate cortices associated with self-referential processing and the subgenual anterior cingulate and neighboring medial frontal cortices) with lateral prefrontal areas related to externally-directed cognition. Other areas of hyperactivity/hyperconnectivity include the left lateral parietal cortex, right hippocampus and right cerebellum whereas hypoactivity/hypoconnectivity was observed mainly in the left temporal cortex, the insula, precuneus, superior frontal gyrus, lentiform nucleus and thalamus. Results are made available in two different data formats to be used as spatial hypotheses in future studies, particularly for diagnostic classification by MVPA.