Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of transport proteins in drug absorption, distribution and excretion

1. The molecular and functional characterization of transport proteins is emerging rapidly and significant numbers of drugs have been shown to be substrates or inhibitors. The purpose of this review is to highlight the in vivo preclinical and clinical evidence that supports a role for transport proteins in attenuating the absorption, distribution and excretion (ADE) of drugs. 2. For absorption, a clear role has emerged for P-glycoprotein in limiting permeability across the gastrointestinal tract. As a result, a wide variety of drugs suffer from incomplete, variable and non-linear absorption. Similarly, at the blood-brain barrier a range of drugs has limited brain penetration due to P-glycoprotein-mediated efflux, which can limit therapeutic effectiveness of CNS agents. In the liver, transport proteins are present on the sinusoidal membrane that can be the rate-limiting step in hepatic clearance for some drugs. Mechanistic studies clearly suggest a key role and broad substrate specificity for the OATP family of sinusoidal transporters. Mainly ATP-dependent transport proteins such as P-glycoprotein and MRP2 govern active biliary excretion. 3. Drug-drug interactions have been demonstrated involving inhibition or induction of transport proteins. Clinically significant interactions in the gastrointestinal tract and kidney have been observed with inhibitors such as ketoconazole, erythromycin, verapamil, quinidine, probenecid and cimetidine. Clinically significant inhibition at the blood-brain barrier is more difficult to demonstrate, relying on pharmacodynamic and toxicodynamic changes, but an example is quinidine increasing loperamide-induced central effects in humans. 4. This review highlights the emerging role of transport proteins in ADE of drugs and suggests these need to be considered, in drug discovery and development, with respect to variability in drug disposition and response.
On the Equivalence of Constraint Satisfaction Problems

A solution of a Constraint Satisfaction Problem (CSP) is an assignment of values to all its variables such that all its constraints are satis ed. Usually two CSPs are considered equivalent if they have the same solution set. We nd this de nition limiting, and develop a more general de nition based on the concept of mutual reducibility. In this extended scheme it is reasonable to consider a pair of CSPs equivalent even if they have di erent solutions. The basic idea behind the extended scheme is that two CSPs can be considered equivalent whenever they contain the same \amount of information", i.e. whenever it is possible to obtain the solution of one of them from the solution of the other one, and viceversa. In this way, both constraint and variable redundancy are allowed in CSPs belonging to the same equivalence class. As an example of the usefulness of this new notion of equivalence, we formally prove that binary and non-binary CSPs are equivalent (in the new sense). Such a proof is not possible with the usual notion of equivalence. Two di erent algorithms, currently used for transforming any non-binary CSP into an equivalent binary one, are described. It turns out that only one of them produces a binary CSP equivalent to the given non-binary problem, while the other one can achieve the transformation only at the cost of adding some new arbitrary information.
Alcohol‐responsive myoclonic dystonia in a large family: Dominant inheritance and phenotypic variation

Alcohol‐responsive myoclonic dystonia is reported in 26 individuals in a six‐generation family, thus indicating autosomal dominant inheritance. Twenty affected family members aged between 3 and 56 years were examined on one occasion. Myoclonus in arms, shoulder, and neck distribution was seen in 17, with occasional generalized jerks in 14. Leg dystonia/hemidystonia was seen in two infant cases, writer's cramp in seven, torticollis/retrocollis in two, and finger tremor in three. The onset of myoclonus was regularly reported from 2 to 3 years of age, the onset of leg dystonia/hemidystonia from 6 to 18 months of age, writer's cramp from early school age, and neck dystonia from late teenage. The effect of alcohol had been noted in 10 individuals, and seven of them abused alcohol. Once established, the neurological signs did not progress significantly. Leg dystonia resolved in two juvenile members. Two adult members had recovered from myoclonus: one elderly man and one posthemorrhagic spastic hemiplegic man. Extensive family investigation is necessary to clarify the clinical variation of this autosomal dominant disorder of involuntary movements.
Optimal control of a single link flexible manipulator

An exact state-space dynamic model for manipulator with flexible links is considered. The Bernoulli-Euler beam equations are used to derive a frequency domain matrix transfer function. This transfer function is then used to computer the Laplace transform of the state vector as a function of lateral position along a single link manipulator. The problem of optimal end-point control of the beam is addressed. A sixth-order state-space model is derived for the manipulator and the controller is based on this model. Several control laws are studied for this model. The manipulator is modeled as eighth-order, but the control law based on the sixth-order model is retained. The six states are estimated from the output of the eighth-order model. These states are fed back to the controller to derive the control torque used to drive the manipulator. A filter is introduced to compensate for spillover. The results are satisfactory, and are illustrated by simulated case studies. <<ETX>>
Three‐dimensional porous scaffolds at the crossroads of tissue engineering and cell‐based gene therapy

In the last 20 years, more than 1,500 gene therapy clinical trials have been approved worldwide targeting a variety of indications, from inherited monogenic diseases to acquired conditions such as cancer, cardiovascular and infectious diseases. However, concerns about the safety and efficacy of gene therapy pharmaceuticals justify the development of alternative strategies to ensure the clinical translation of this still promising field. In particular, ex vivo gene therapy strategies using autologous adult stem cells coupled to three‐dimensional (3D) porous scaffolds show great promises in preclinical studies. Developments in the fields of biomaterial sciences and tissue engineering have already helped understanding how we can harness to regenerative potential of many cell types to create artificial tissues and organs and vastly improve the engraftment of ex vivo manipulated adult stem cells. In this article, we will review the current state of the art in tissue engineering by exploring the various types of clinically available biomaterials and the methods used to process them into complex 3D scaffolds. We will then review how these technologies are applied in cell‐based gene therapy and identify novel avenues of research that may benefit patients in the near future. J. Cell. Biochem. 108: 537–546, 2009. © 2009 Wiley‐Liss, Inc.
Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

Objective:To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. Design:Prospective, observational study. Setting:Mixed intensive care unit of a 900-bed university hospital. Patients:Thirty-eight consecutive adult patients with septic shock and acute lung injury. Interventions:None. Measurements and Main Results:The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (≥7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r = −.48, p = .002), Pao2/Fio2 (r = −.50, p = .001), lung injury score (r = .46, p = .004), roentgenogram quadrants (r = .39, p = .02), and platelet count (r = −.43, p = .007). At day 3, EVLWI correlated with compliance (r = −.51, p = .002), Pao2/Fio2 (r = −.49, p = .006), and lung injury score (r = .53, p = .003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p< .05). The plasma concentration of endothelin-1 (mean ± sd) was significantly higher in patients with elevated EVLWI (≥7 mL/kg) (3.85 ± 1.40 vs. 2.07 ± 0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. Conclusions:In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.
State Rumination: Associations with Emotional Stress Reactivity and Attention Biases

Within dysphoria, rumination has been identified as a particularly maladaptive emotion regulation strategy linked to prolonged negative affect and the onset of depressive episodes. Until now, the majority of research assessing naturally occurring rumination has utilized trait rumination measures; however, additional information may be obtained by assessing state rumination. The current study examined the association between state rumination and participants' emotional recovery from stress. In addition, biased attention toward emotional information was investigated as a mechanism that might underlie state rumination. Participants completed the exogenous cuing task to assess attentional engagement and disengagement from emotional facial expressions followed by a psychosocial stressor. State rumination and self-reported sadness were measured during the recovery period. As expected, state rumination was associated with less recovery in sadness scores, even after controlling for trait rumination and depressive symptoms. Moreover, within the high dysphoria group, participants who had more difficulty disengaging from emotional expressions reported higher levels of rumination in response to the stressor. Results highlight an important association between state rumination and individuals' recovery from stress, and suggest that difficulty disengaging attention from emotional expressions might be one mechanism underlying state rumination in dysphoria.
Obstacles and Pedestrian Detection on a Moving Vehicle

We present a new method for obstacle and pedestrian detection with lower computation complexity and higher detection performance on a small target. By calculating stereo disparity according to the road parameters, our system efficiently detects objects above the ground. Experiments on over 10,000 images captured in urban areas demonstrate our method's effectiveness. We also propose a multi-scale compatible pedestrian detector. Detection speed is improved by avoiding size adjustment of input. Experiments on three public pedestrian databases and our HENU database show that our detector achieves better results than the state-of-the-art detection quality at equal speed, especially on pedestrian target with small size.
Origin and partial characterization of Fc receptor‐bearing cells found within experimental carcinomas and sarcomas

A variety of marine connective and epithelial tissue tumors, including the SAD/2 and FS9 fibrosarcomas, the TA3/Ha and CAD/2 mammary carcinomas and a primary methylcholanthrene‐induced sarcoma, were found to contain a high proportion of cells with receptors for the Fc portion of immunoglobulin G (“Fc receptors”). Experiments were undertaken to assess whether these cells were neoplastic, or whether they represented the infiltration into the tumor of non‐malignant host cells such as macro‐phages or lymphocytes. It was found that long‐term established in vitro cell lines of the TA3/Ha SAD/2 and CAD/2 tumors were entirely negative for the Fc receptor, whereas injection of these cells led to the formation of tumors containing a high proportion of Fc receptor‐bearing cells. Many of these cells were actively phagocytic as assessed by ingestion of iron filings or antibody‐coated erythrocytes. Injection of Fc receptor‐negative cultured tumor cells into F1 hybrids, in which host cells could be distinguished from the tumor cells by anti‐H2 sera, revealed that many or all of the Fc receptor‐bearing cells in the resultant tumor were of host origin. In contrast to its effect on normal spleen cells, anti‐θ serum treatment also partially inhibited Fc rosettes, suggesting a T‐lymphocyte origin for some of the Fc receptor‐bearing cells. Since almost all cells with potential anti‐tumor activity bear Fc receptors, it is suggested that an index of host cell infiltration of carcinomas and sarcomas can quickly and easily be ascertained by enumeration of Fc receptor‐bearing cells.
A 12-kVA DSP-Controlled Laboratory Prototype UPQC Capable of Mitigating Unbalance in Source Voltage and Load Current

This paper reports the development of a laboratory prototype of a fully digital DSP-controlled 12-kVA unified power quality conditioner (UPQC), capable of compensating for both the supply voltage and the load current imperfections. A fully digital controller based on the TMS320F2812 DSP platform is implemented for the reference generation as well as control purposes. The delay problem in the digital controller is overcome by application of a fast DSP, a compact control technique and proper flow of control steps in the DSP software. A phase-locked loop-less software grid synchronization method has been implemented for the effective operation of the UPQC under conditions of grid frequency variation. A sequence-based compensation strategy has been developed to compensate for balanced and unbalanced sags while accommodating the fact that the voltage injection capability of the UPQC is limited. The prototype UPQC power circuit, control features, and control algorithm along with experimental results are presented in this paper.
Speech recognition using noise-adaptive prototypes

A probabilistic mixture model is described for a frame (the short-term spectrum) of each to be used in speech recognition. Each component of the mixture is regarded as a prototype for the labeling phase of a hidden Markov model based speech recognition system. Since the ambient noise during recognition can differ from the ambient noise present in the training data, the model is designed for convenient updating in changing noise. Based on the observation that the energy in a frequency band is at any fixed time dominated either by signal energy or by noise energy, the authors model the energy as the larger of the separate energies of signal and noise in the band. Statistical algorithms are given for training this as a hidden variables model. The hidden variables are the prototype identities and the separate signal and noise components. A series of speech recognition experiments that successfully utilize this model is also discussed. <<ETX>>
Overlap cooperative spectrum sensing with energy comparing in cognitive radio networks

In cognitive radio network, cooperation multiple secondary users can improve the performance of spectrum sensing. However, the sensing process duration is generally increasing because the number of the local decisions needing to be sent to the fusion center. Most alternative works consider a general time frame structure in which all the cognitive radio users (CRs) sense the signal in the same time and then each user must waits for its turn to report its observation. Hence, there is a waste of the time here and this time consumed by waiting can contribute little to the performance of spectrum sensing. In this paper, we propose an overlap spectrum sensing, the CRs keep collecting and fusing the signal while another is reporting to FC. By making use of the waiting time for sensing, the new framework provides a much wider observing window for spectrum measurement, which results in a performance improvement of spectrum sensing. Besides, we also apply the energy comparing to choose the good CR to send its local decision in each reporting time slot. The sensing performances of this sensing strategy are analyzed and confirmed by the Monte-Carlo simulation results.
Accounting for subliminal priming in ACT-R.

This paper presents a cognitive model of a subliminal priming task, using Retrieval by ACcumulating Evidence (RACE), a model of declarative memory retrieval. RACE is implemented as an extension to the ACT-R architecture of cognition. First, we will discuss the exact implementation of RACE within the constraints imposed by ACT-R. Second, we will discuss the subliminal priming task that we modeled and present a cognitive model of this task that incorporates RACE.
Short Nissl staining for incubated cryostat sections of the brain.

Nissl stain often binds poorly to cryostat sections which have been incubated in solutions of radiolabeled ligands. Such incubation is used in receptor autoradiography of the brain when using the in vitro method. We have developed a rapid (16 min) modification of Nissl staining for sections that bind stain poorly, e.g., incubated sections. The method stains well sections which cannot be stained with other rapid Nissl staining methods.
Carbon doped GaN buffer layer using propane for high electron mobility transistor applications: Growth and device results

The creation of a semi insulating (SI) buffer layer in AlGaN/GaN High Electron Mobility Transistor (HEMT) devices is crucial for preventing a current path beneath the two-dimensional electron gas (2DEG). In this investigation, we evaluate the use of a gaseous carbon gas precursor, propane, for creating a SI GaN buffer layer in a HEMT structure. The carbon doped profile, using propane gas, is a two stepped profile with a high carbon doping (1.5 x 10(18) cm(-3)) epitaxial layer closest to the substrate and a lower doped layer (3 x 10(16) cm(-3)) closest to the 2DEG channel. Secondary Ion Mass Spectrometry measurement shows a uniform incorporation versus depth, and no memory effect from carbon doping can be seen. The high carbon doping (1.5 x 10(18) cm(-3)) does not influence the surface morphology, and a roughness root-mean-square value of 0.43 nm is obtained from Atomic Force Microscopy. High resolution X-ray diffraction measurements show very sharp peaks and no structural degradation can be seen related to the heavy carbon doped layer. HEMTs are fabricated and show an extremely low drain induced barrier lowering value of 0.1 mV/V, demonstrating an excellent buffer isolation. The carbon doped GaN buffer layer using propane gas is compared to samples using carbon from the trimethylgallium molecule, showing equally low leakage currents, demonstrating the capability of growing highly resistive buffer layers using a gaseous carbon source.
Evaluation of a whole blood remote platelet function test for the diagnosis of mild bleeding disorders

Mild platelet function disorders (PFDs) are complex and difficult to diagnose. The current gold standard test, light transmission aggregometry (LTA), including lumi‐aggregometry, is time and labour intensive and blood samples must be processed within a limited time after venepuncture. Furthermore, many subjects with suspected PFDs do not show a platelet abnormality on LTA.
Regional differences in white matter breakdown between frontotemporal dementia and early-onset Alzheimer's disease.

BACKGROUND White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). OBJECTIVE Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. METHODS We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. RESULTS Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. CONCLUSIONS The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group.
A binomial noised model for cluster validation

Cluster validation is the task of estimating the quality of a given partition of a data set into clusters of similar objects. Normally, a clustering algorithm requires a desired number of clusters as a parameter. We consider the cluster validation problem of determining the optimal “true” number of clusters. We adopt the stability testing approach, according to which, repeated applications of a given clustering algorithm provide similar results when the specified number of clusters is correct. To implement this idea, we draw pairs of independent equal sized samples, where one sample in any pair is drawn from the data source and the other one is drawn from a noised version thereof. We then run the same clustering method on both samples in any pair and test the similarity between the obtained partitions using a general k-Nearest Neighbor Binomial model. These similarity measurements enable us to estimate the correct number of clusters. A series of numerical experiments on both synthetic and real world data demonstrates the high capability of the offered discipline compared to other methods. In particular, the use of a noised data set is shown to produce significantly better results than in the case of using two independent samples which are both drawn from the data source.