Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of the Calibration Standards of Three Commercially Available Multiplex Kits for Human Cytokine Measurement to WHO Standards Reveals Striking Differences

Serum parameters as indicators for the efficacy of therapeutic drugs are currently in the focus of intensive research. The induction of certain cytokines (or cytokine patterns) is known to be related to the status of the immune response e.g. in regulating the TH1/TH2 balance. Regarding their potential value as surrogate parameters in clinical trials and subsequently for the assignment of treatment efficacy, the accurate and reliable determination of cytokines in patient serum is mandatory. Because serum samples are precious and limited, test methods–-like the xMAP multiplex technology–-that allow for the simultaneous determination of a variety of cytokines from only a small sample aliquot, can offer great advantages. We here have compared multiplex kits from three different manufactures and found striking differences upon standardizing using WHO standards for selected cytokines. We therefore extended our xMAP multiplex measurements investigations to an ex-vivo situation by testing serum samples and found that the cytokine amounts measured was critically influenced by the actual kit used. The presented data indicate that statements regarding the quantitive determination of cytokines–-and therefore their use as biomarkers–-in serum samples have to be interpreted with caution.
Reentrant Processing in Intuitive Perception

The process of perception requires not only the brain's receipt of sensory data but also the meaningful organization of that data in relation to the perceptual experience held in memory. Although it typically results in a conscious percept, the process of perception is not fully conscious. Research on the neural substrates of human visual perception has suggested that regions of limbic cortex, including the medial orbital frontal cortex (mOFC), may contribute to intuitive judgments about perceptual events, such as guessing whether an object might be present in a briefly presented fragmented drawing. Examining dense array measures of cortical electrical activity during a modified Waterloo Gestalt Closure Task, results show, as expected, that activity in medial orbital frontal electrical responses (about 250 ms) was associated with intuitive judgments. Activity in the right temporal-parietal-occipital (TPO) region was found to predict mOFC (∼150 ms) activity and, in turn, was subsequently influenced by the mOFC at a later time (∼300 ms). The initial perception of gist or meaning of a visual stimulus in limbic networks may thus yield reentrant input to the visual areas to influence continued development of the percept. Before perception is completed, the initial representation of gist may support intuitive judgments about the ongoing perceptual process.
Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase

D-amino acid oxidase (DAAO) catalyzes the oxidative deamination of several neutral D-amino acids and is the enzyme mainly responsible (together with serine racemase) for degrading D-serine (D-Ser) in the central nervous system of mammals. This D-amino acid, which binds the coagonist site of the N-methyl-D-aspartate receptor, is thus a key neuromodulator of glutamatergic neurotransmission. Altered D-Ser metabolism results in several pathological conditions (e.g., amylotrophic lateral sclerosis or schizophrenia, SZ) for which effective “broad spectrum” pharmaceutical drugs are not yet available. In particular, the correlation between reduced D-Ser concentration and SZ led to a renaissance of biochemical interest in human DAAO (hDAAO). In the last 10 years, public and corporate research laboratories undertook huge efforts to study the structural, enzymatic, and physiological properties of the human flavoenzyme and to identify novel effective inhibitors which, acting as pharmaceutical drugs, could decrease hDAAO activity, thus restoring the physiological concentration of D-Ser. Although, none of the identified hDAAO inhibitors has reached the market yet, from a biochemical point of view, these compounds turned out to be invaluable for gaining a detailed understanding of the structure/function relationships at the molecular level in the mammalian DAAO, in particular of the interaction between ligand and the enzyme. This detailed knowledge, together with several recent studies concerning the interaction of the human enzyme with other protein regulative partners, its subcellular localization, and in vivo degradation, contributed to gaining comprehensive knowledge of the structure, function, and physiopathological role of this important human enzyme.
Multiple-Instance Learning for Medical Image and Video Analysis

Multiple-instance learning (MIL) is a recent machine-learning paradigm that is particularly well suited to medical image and video analysis (MIVA) tasks. Based solely on class labels assigned globally to images or videos, MIL algorithms learn to detect relevant patterns locally in images or videos. These patterns are then used for classification at a global level. Because supervision relies on global labels, manual segmentations are not needed to train MIL algorithms, unlike traditional single-instance learning (SIL) algorithms. Consequently, these solutions are attracting increasing interest from the MIVA community: since the term was coined by Dietterich et al. in 1997, 73 research papers about MIL have been published in the MIVA literature. This paper reviews the existing strategies for modeling MIVA tasks as MIL problems, recommends general-purpose MIL algorithms for each type of MIVA tasks, and discusses MIVA-specific MIL algorithms. Various experiments performed in medical image and video datasets are compiled in order to back up these discussions. This meta-analysis shows that, besides being more convenient than SIL solutions, MIL algorithms are also more accurate in many cases. In other words, MIL is the ideal solution for many MIVA tasks. Recent trends are discussed, and future directions are proposed for this emerging paradigm.
Prevention and treatment of hand oedema after stroke

Abstract Purpose: As there is no evidence for a specific treatment for post–stroke-induced hand oedema, rehabilitation centre Blixembosch formalized a best practice protocol. We investigated whether the Blixembosch hand oedema protocol is usable in daily practice and leads to lower incidence (prevention) and shorter duration (treatment) compared with care as usual. Methods: In a non-randomised comparative trial, we investigated 206 post-stroke patients admitted to two Dutch rehabilitation centres. Hand volumes were measured at least bi-weekly using a volumeter. Treatment was started according the protocol (Blixembosch) or following care as usual (Leijpark). Usability was assessed with a survey among professionals. Results: In the Blixembosch group, 16% developed oedema after admission, compared with 21% in the control group (p = 0.019). Average duration of oedema (both developed before and after admission) was 6.5 weeks in the Blixembosch group compared with 3.1 weeks in the control group (p = 0.000). Professionals were positive about the protocol. Conclusion: The study showed that the protocol is usable in daily practice and has a small beneficial effect on hand oedema incidence rates compared with care as usual. The negative effect on duration of hand oedema could also be caused by the difference in prognosis between the two groups. Implications for Rehabilitation Hand oedema after stroke: Hand oedema often appears early after stroke. Preventive measures seem to reduce the incidence of hand oedema and should be promoted also in admitting hospitals. Age and reduced hand motor function are related to incidence of hand oedema.
A comparison of anterior compartment pressures in competitive runners and cyclists

Anterior compartment pressure was measured in 10 competitive runners and in 10 competitive cyclists who were asymptomatic for compartment syndrome. Pres sures were measured at rest, after exercise at 80% VO2max, after maximal exercise, and 15 minutes after both exercise bouts. No difference in compartment pressure was found after exercise at 80% VO2max in runners and cyclists. Total creatine phosphokinase en zyme levels measured before and after exercise at 80% VO2max showed a 1 0-fold increase in runners as com pared to cyclists. Anterior compartment pressure meas ured after maximal exercise was significantly greater in runners as compared to cyclists. Compartment pres sure showed no increase from resting values during cycling at 80% VO2max or maximal exercise. These findings suggest that patients with chronic anterior compartment syndrome may be able to cycle without elevation of compartment pressure and concomitant pain as an alternative exercise to maintain a continued degree of fitness and training. Compartment pressures should be measured during cycling in patients with chronic compartment syndrome to determine its effi cacy as a method for maintenance of cardiorespiratory fitness.
Visual problems of new malaysian drivers.

PURPOSE The objective of this study was to determine the prevalence of poor visual acuity, colour blindness and visual field defect of new Malaysian drivers. METHODS A total of 3717 new drivers (50.2% males and 49.8% females) age 19±6 years, voluntarily participated in this study. Standard optometric apparatus such as LogMAR Charts, Ishihara plates and HandHeld Bernell Perimeter were used and standard procedures were applied. RESULTS The visual examination showed 6.7% (n=250) of subjects achieved less than 0.3 LogMAR with better eye whilst 2.2% (n=83) had failed the Ishihara Test (2.1% males and 0.1% females). Most of the affected drivers were deutranopia. Only 2094 subjects had their visual field using a mobile Handheld Bernell Perimeter. 1.72% (n=36) subjects have less than 120 degrees of peripheral field of vision. CONCLUSIONS The visual status among new Malaysian drivers needs to be taken seriously to ensure safe driving. Other factors such as colour vision and visual field screening have to be considered seriously when evaluating the visual performance of a driver. Good visual performance is indispensible for safe driving.
Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells

ABSTRACT Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major replicase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral replicase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex.
Mineralization of Nitrogen in Soils Amended with Dairy Manure as Affected by Wetting/Drying Cycles

Abstract Interest in manure management and its effects on nitrogen (N) mineralization has increased in recent years. The focus of this research was to investigate the N‐mineralization rates of different soil types in Coastal Plain soils and compare them to a soil from Illinois. Soils with and without dairy composted manure addition were subjected to different wetting/drying cycles [constant moisture at 60% water‐filled pore space (WFPS) and cycling moisture from 60 to 30% WFPS] under laboratory conditions at three different temperatures (11°C, 18°C, and 25°C). Samples were collected from three different soil types: Catlin (Mollisols), Bama (Ultisols), and Goldsboro (Utilsols). Soil chemical and physical properties were determined to help assess variations in N-mineralization rates. Addition of composted manure greatly impacted the amount of N mineralized. The amount of manure‐derived organic N mineralized to inorganic forms was mainly attributed to the soil series, with the Catlin (silt loam) producing the most inorganic N followed by the Goldsboro (loam) and then Bama (sandy loam). This was probably due to soil texture and the native climatic conditions of the soil. No significant differences were observed between the constant and cycling moisture regimens, suggesting that the imposed drying cycle may not have been sufficient to desiccate microbial cells and cause a flush in N mineralization upon rewetting. Nitrogen mineralization responded greatly to the influence of temperature, with the greatest N mineralization occurring at 25°C. The information acquired from this study may aid in predicting the impact of manure application to help increase N‐use efficiency when applied under different conditions (e.g., climate season) and soil types.
Tactile Stimulation Evokes Long-Term Synaptic Plasticity in the Granular Layer of Cerebellum

Several forms of long-term synaptic plasticity [long-term potentiation (LTP) and long-term depression (LTD)] have been reported in the cerebellar circuit in vitro, but their determination in vivo was still lacking in most cases. Here we show that, in the urethane-anesthetized rat, appropriate patterns of facial tactile stimulation as well as intracerebellar electrical stimulation can induce LTP and LTD in local field potentials recorded from the granular layer of Crus-IIa. LTD prevailed in control conditions, whereas LTP prevailed during local application of gabazine. No relevant plasticity was observed when gabazine and APV were coapplied. The pharmacological and kinetic properties of LTP and LTD in vivo were compatible with those reported in the granule cell layer in vitro (Mapelli and D'Angelo, 2007), suggesting that NMDA receptor-dependent plasticity was generated at the mossy fiber–granule cell synapse under the inhibitory control of the Golgi cell circuit. Interestingly, LTP and LTD were able to regulate the response latency to tactile stimulation, as expected from computational modeling of the expression mechanisms (Nieus et al., 2006). This result suggests that LTP and LTD could regulate the spatiotemporal pattern of granular layer responses to mossy fiber inputs.
Entropy-based statistical analysis of eye movement transitions

The paper introduces a two-step method of quantifying eye movement transitions between Areas of Interests (AOIs). First, individuals' gaze switching patterns, represented by fixated AOI sequences, are modeled as Markov chains. Second, Shannon's entropy coefficient of the fit Markov model is computed to quantify the complexity of individual switching patterns. To determine the overall distribution of attention over AOIs, the entropy coefficient of individuals' stationary distribution of fixations is calculated. The novelty of the method is that it captures the variability of individual differences in eye movement characteristics, which are then summarized statistically. The method is demonstrated on gaze data collected during free viewing of classical art paintings. Shannon's coefficient derived from individual transition matrices is significantly related to participants' individual differences as well as to their aesthetic experience of art pieces.
Design of a doubly-fed reluctance motor for adjustable speed drives

A methodology for steady-state performance analysis and design of the doubly-fed reluctance motor (DFRM) is presented in this paper. Emphasis is placed on the linear model of the DFRM, but magnetic nonlinearities are also characterized. A prototype 2 HP DFRM is designed and built in comparison with an induction motor. Performance of the prototype 2 HP DFRM motor is analyzed thoroughly and is supported by actual measurements, wherever available. <<ETX>>
Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice

Although primary cilia are well established as important sensory and signaling structures, their function in most tissues remains unknown. Obesity is a feature associated with some syndromes of cilia dysfunction, such as Bardet-Biedl syndrome (BBS) and Alström syndrome, as well as in several cilia mutant mouse models. Recent data indicate that obesity in BBS mutant mice is due to defects in leptin receptor trafficking and leptin resistance. Furthermore, induction of cilia loss in leptin-responsive proopiomelanocortin neurons results in obesity, implicating cilia on hypothalamic neurons in regulating feeding behavior. Here, we directly test the importance of the cilium as a mediator of the leptin response. In contrast to the current dogma, a longitudinal study of conditional Ift88 cilia mutant mice under different states of adiposity indicates that leptin resistance is present only when mutants are obese. Our studies show that caloric restriction leads to an altered anticipatory feeding behavior that temporarily abrogates the anorectic actions of leptin despite normalized circulating leptin levels. Interestingly, preobese Bbs4 mutant mice responded to the anorectic effects of leptin and did not display other phenotypes associated with defective leptin signaling. Furthermore, thermoregulation and activity measurements in cilia mutant mice are inconsistent with phenotypes previously observed in leptin deficient ob/ob mice. Collectively, these data indicate that cilia are not directly involved in leptin responses and that a defect in the leptin signaling axis is not the initiating event leading to hyperphagia and obesity associated with cilia dysfunction.
Genomic Characterization of the Novel Aeromonas hydrophila Phage Ahp1 Suggests the Derivation of a New Subgroup from phiKMV-Like Family

Aeromonas hydrophila is an opportunistic pathogenic bacterium causing diseases in human and fish. The emergence of multidrug-resistant A. hydrophila isolates has been increasing in recent years. In this study, we have isolated a novel virulent podophage of A. hydrophila, designated as Ahp1, from waste water. Ahp1 has a rapid adsorption (96% adsorbed in 2 min), a latent period of 15 min, and a burst size of 112 PFU per infected cell. At least eighteen Ahp1 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 36-kDa protein being the predicted major capsid protein. Genome analysis of Ahp1 revealed a linear doubled-stranded DNA genome of 42,167 bp with a G + C content of 58.8%. The genome encodes 46 putative open reading frames, 5 putative phage promoters, and 3 transcriptional terminators. Based on high degrees of similarity in overall genome organization and among most of the corresponding ORFs, as well as phylogenetic relatedness among their DNAP, RNAP and major capsid proteins, we propose a new subgroup, designated Ahp1-like subgroup. This subgroup contains Ahp1 and members previously belonging to phiKMV-like subgroup, phiAS7, phi80-18, GAP227, phiR8-01, and ISAO8. Since Ahp1 has a narrow host range, for effective phage therapy, different phages are needed for preparation of cocktails that are capable of killing the heterogeneous A. hydrophila strains.
Validation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: implications for virus design and delivery.

Motivated by the rapid expansion in the development of replication-competent viral agents for the treatment of solid tumors, we formulated and analyzed a three-dimensional mathematical model of a tumor that is infected by a replication-competent virus. We initially considered three patterns of intratumoral injection in which a fixed fraction of cells are initially infected with the virus throughout (a) the entire tumor, (b) the tumor core, and (c) the tumor rim, respectively. For each injection pattern, an approximate analysis of the model provides a simple and accurate condition for whether the virus will eradicate the tumor. The model was then generalized to incorporate nutrient-limited necrosis and an innate immune response against virus-infected tumor cells. Recent preclinical and clinical data were used to validate the model and estimate key parameter values. Our analysis has the following implications: even in the absence of an immune response, tumor eradication requires widespread distribution of the virus within the tumor at the time of infection; core or rim injections alone may result in tumor escape, particularly in a well-vascularized tumor; the more rapidly a virus lyses infected cells the more effective it will be at controlling the tumor; and the innate immune response to the virus can potentially prevent the virus from controlling the tumor, even with repeat injections. Therefore, in addition to diffuse intratumoral infection, tumor eradication by oncolytic adenovirus will probably require potent suppression of innate immune clearance mechanisms (e.g., by replacement of adenovirus E3 genes), combinations with traditional (chemotherapy, radiotherapy) treatments, and/or concomitant therapeutic gene expression with resultant bystander effects.
Does Contracting Out Increase the Efficiency of Government Programs? Evidence from Medicaid Hmos

State governments contract with health maintenance organizations (HMOs) to coordinate medical care for nearly 20 million Medicaid recipients. Identifying the causal effect of HMO enrollment on government spending and health care quality is difficult if, as is often the case, recipients have the option to enroll in a plan. To estimate the average effect of HMO enrollment, this paper exploits county-level mandates introduced during the last several years in the state of California that required most Medicaid recipients to enroll in a managed care plan. The empirical results demonstrate that the resulting switch from fee-for-service to managed care was associated with a substantial increase in government spending but no observable improvement in health outcomes, thus apparently reducing the efficiency of this large government program. The findings cast doubt on the hypothesis that HMO contracting has reduced the strain on government budgets.
Bidder's strategy under group-buying auction on the Internet

The group-buying auction is a new kind of dynamic pricing mechanism on the Internet. It is a variant of the sellers' price double auction, which makes the bidders as a group through Internet to get the volume discounts, i.e., the more bidders bid, the lower the price of the object being auctioned becomes. In this paper, we analyze the group-buying auction under some assumptions, such as that the independent private values (IPVs) model applies and bidders are risk neutral and symmetric, etc., and build an incomplete information dynamic game model to illustrate the bidders' bidding process. It proves that for the bidders there exists a weakly dominant strategy S, i.e., no matter when a bidder arrives at the auction and what the bidding history is, the highest permitted bid price that is no greater than his value to the object is always his optimal bid price but may not be the unique one.