Miracle-dz/UniFAR-FTUs huggingface dataset:
Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

Since elevated expression of matrix metalloproteinase (MMP)-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH2 (GK8) as spacer between α-tocopherol succinate (α-TOS) and methoxy-polyethylene glycol molecular weight (MW 2000 Da) activated by N-hydroxysuccinimide (mPEG2K-NHS), mPEG2K-GK8-α-TOS (TGK) was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and TGK (n:n =40:60, TGK micelles). mPEG2K-α-TOS (T2K) was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles) owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX)-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC50) of TGK and T2K micelles were similar (P>0.05) in MCF-7 cells (MMP-2/9 underexpression), the IC50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 μg/mL, respectively, in HT1080 cells (MMP-2/9 overexpression). The MMP-2/9-sensitive micelles also demonstrated desired tumor targeting and accumulation ability in vivo. The results of in vivo antitumor effect evaluation indicate that TGK micelles are potent against solid tumors while maintaining minimum systemic toxicity compared with T2K micelles and DTX.
Face Recognition using Laplacian+OPRA-faces

We propose a face recognition method named the Laplacian+OPRA-faces approach based on the Laplacian-faces and the OPRA-faces approach. An explicit mapping from the high-dimensional data space to the reduced space is obtained. The method aims to preserve both the local structure of local preserving projections (LLE) and the local geometry of orthogonal projection reduction by affinity (OPRA). Several improved measures and selection method of parameters in the supervised case are presented. We compare the proposed approach with eigenfaces, fisherfaces, Laplacianfaces and OPRA-faces on two different face data sets. Experimental results indicate that Laplacian+OPRA-faces are better than Laplacianfaces and OPRA-faces
The Role of Neutrophils in Corneal Wound Healing in HO-2 Null Mice

Our studies demonstrated that Heme oxygenase (HO), in particular, the constitutive HO-2, is critical for a self-resolving inflammatory and repair response in the cornea. Epithelial injury in HO-2 null mice leads to impaired wound closure and chronic inflammation in the cornea. This study was undertaken to examine the possible relationship between HO-2 and the recruitment of neutrophils following a corneal surface injury in wild type (WT) and HO-2 knockout (HO-2−/−) mice treated with Gr-1 monoclonal antibody to deplete peripheral neutrophils. Epithelial injury was performed by removing the entire corneal epithelium. Infiltration of inflammatory cell into the cornea in response to injury was higher in HO-2−/− than in WT. However, the rate of corneal wound closure following neutrophil depletion was markedly inhibited in both WT and HO-2−/− mice by 60% and 85%, respectively. Neutropenia induced HO-1 expression in WT but not in HO-2−/− mice. Moreover, endothelial cells lacking HO-2 expressed higher levels of the Midkine and VE-cadherin and displayed strong adhesion to neutrophils suggesting that perturbation in endothelial cell function caused by HO-2 depletion underlies the increased infiltration of neutrophils into the HO-2−/− cornea. Moreover, the fact that neutropenia worsened epithelial healing of the injured cornea in both WT and HO-2−/− mice suggest that cells other than neutrophils contribute to the exaggerated inflammation and impaired wound healing seen in the HO-2 null cornea.
Media consumption and crime trend perceptions: a longitudinal analysis

ABSTRACT For over two decades, despite the downward crime trend, the American public has persisted in believing crime is on the rise. Cultivation theory holds that the media is responsible for the public’s crime trend perceptions. Previous cultivation studies heavily rely on cross-sectional data, which may lead to spurious conclusions due to reverse causation and omitted variable bias. This study aims to address these issues by utilizing longitudinal analyses. Drawing on three waves of the 2008–2009 American National Election Survey, we test the cultivation hypothesis using traditional OLS, OLS with lagged crime trend perceptions, fixed effects, and dynamic panel models. Newspaper and TV news consumption are related to crime trend perceptions in traditional OLS models. In other models, media consumption is not related to crime trend perceptions. The results do not support the cultivation hypothesis. It is likely that the cultivation effect of media has been overstated in the previous cross-sectional research.
Controlling social desirability bias

Social desirability bias can change the results from marketing experiments and surveys. However, there are few illustrations that show how serious social desirability bias can be. This research starts by reviewing the options for identifying and reducing social desirability bias in experiments and surveys and for controlling its effects. Then two examples that use a social desirability bias scale or a transformation of it (that may improve its utility) as control variables are described. Data from a national panel survey in the United States is used to show that controlling social desirability bias can change the set of demographic variables that are judged to be statistically significant and can have important effects on coefficient sizes. These illustrations will hopefully stimulate more consideration of social desirability bias, more use of bias measures in marketing studies, and more research on the control options.
Analyzing Weighted  $\ell_1$ Minimization for Sparse Recovery With Nonuniform Sparse Models

In this paper, we introduce a nonuniform sparsity model and analyze the performance of an optimized weighted ℓ1 minimization over that sparsity model. In particular, we focus on a model where the entries of the unknown vector fall into two sets, with entries of each set having a specific probability of being nonzero. We propose a weighted ℓ1 minimization recovery algorithm and analyze its performance using a Grassmann angle approach. We compute explicitly the relationship between the system parameters-the weights, the number of measurements, the size of the two sets, the probabilities of being nonzero-so that when i.i. d. random Gaussian measurement matrices are used, the weighted ℓ1 minimization recovers a randomly selected signal drawn from the considered sparsity model with overwhelming probability as the problem dimension increases. This allows us to compute the optimal weights. We demonstrate through rigorous analysis and simulations that for the case when the support of the signal can be divided into two different subclasses with unequal sparsity fractions, the weighted ℓ1 minimization outperforms the regular ℓ1 minimization substantially. We also generalize our results to signal vectors with an arbitrary number of subclasses for sparsity.
The school experiences of mixed-race white and black Caribbean children in England

ABSTRACT This research aims to explore the school experiences of mixed white/ black Caribbean children in English schools. The overarching findings of this research confirm that although the mixed-race population as a whole is achieving above the national average, the mixed white/ black Caribbean group is consistently the lowest performing mixed-race group in the country. Views of pupils, their parents and teachers in two London secondary schools suggest various reasons why mixed white/ black Caribbean pupils might continue to be the lowest performing mixed group in the country. These included experiences of marginalization and invisibility in school life, the low expectations that teachers held about them, the lack of knowledge about how to support them at school and how all these issues were exacerbated by the friendship groups they mixed in. This research paper discusses these critical factors in detail and their implications for policy and further research.
Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss

Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a−/+, Efr3a KD) and their wild type littermates. Functional examination showed that both groups of mice suffered from serious hearing loss with a higher level of severity in wild type (WT) mice. Morphologic observation following drugs administration showed that both WT and Efr3a KD mice went through progressive loss of hair cells and SGNs, in association with degenerative changes in the perikarya, intracellular organelles, cell body conformation in SGNs, and the changes of SGNs in WT mice were more severe than in Efr3a KD mice. These beneficial effects of Efr3a KD could be ascribed to an increase in the expression of some neurotrophic factors and their receptors in Efr3a KD mice. Our results indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration in association with an increase in the expression of some neurotrophic factors and their receptors, which may be targeted in the treatment of neurodegeneration.
Clinical presentation and outcome of patients with early, intermediate and late reperfusion therapy by primary coronary angioplasty for acute myocardial infarction.

BACKGROUND Reperfusion therapy by primary coronary angioplasty has been shown to be beneficial for patients who present themselves up to 12 h after the onset of symptoms. However, the relationship between outcome and ischaemic time for patients who present relatively late after the onset of symptoms is still uncertain. The aim of this study was to investigate differences in patient characteristics, left ventricular function and clinical outcome among early (< 3 h), intermediate (3-6 h) and late (6-24 h) treated patients. METHODS AND RESULTS From August 1990 until December 1995, we studied 496 patients who underwent primary coronary angioplasty for acute myocardial infarction. Patients who underwent reperfusion therapy between 6 and 24 h were more often of female gender and more often had diabetes. Primary coronary angioplasty was less successful with later time to reperfusion. Patients who had reperfusion therapy within 6 h showed recovery of left ventricular function at 6 months follow-up, while the left ventricular function of patients treated late had deteriorated. Reocclusion of the infarct-related vessel at follow-up coronary angiography was highest for patients with an ischaemic time of more than 6 h. They more often suffered a repeat myocardial infarction and had a significantly higher 6 months mortality. After adjustment for age, heart rate at presentation, gender, and the presence of diabetes by multi-variate analysis, ischaemic time remained an independent predictor of both left ventricular function recovery and 6 month mortality. CONCLUSIONS The time from symptom onset to reperfusion is related to some baseline clinical characteristics, procedural success rate, left ventricular function and clinical outcome.
Disrupted Small-World Brain Networks in Moderate Alzheimer's Disease: A Resting-State fMRI Study

The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.
Mechanisms of Action Selection and Timing in Substantia Nigra Neurons

The timing of actions is critical for adaptive behavior. In this study we measured neural activity in the substantia nigra as mice learned to change their action duration to earn food rewards. We observed dramatic changes in single unit activity during learning: both dopaminergic and GABAergic neurons changed their activity in relation to behavior to reflect the learned instrumental contingency and the action duration. We found the emergence of “action-on” neurons that increased firing for the duration of the lever press and mirror-image “action-off” neurons that paused at the same time. This pattern is especially common among GABAergic neurons. The activity of many neurons also reflected confidence about the just completed action and the prospect of reward. Being correlated with the relative duration of the completed action, their activity could predict the likelihood of reward collection. Compared with the GABAergic neurons, the activity of dopaminergic neurons was more commonly modulated by the discriminative stimulus signaling the start of each trial, suggesting that their phasic activity reflected sensory salience rather than any reward prediction error found in previous work. In short, these results suggest that (1) nigral activity is highly plastic and modified by the learning of the instrumental contingency; (2) GABAergic output from the substantia nigra can simultaneously inhibit and disinhibit downstream structures, while the dopaminergic output also provide bidirectional modulation of the corticostriatal circuits; (3) dopaminergic and GABAergic neurons show similar task-related activity, although DA neurons are more responsive to the trial start signal.
Differential regulation of gene expression in mouse spermatogonial cells after blocking c-kit-SCF interaction with RNAi

c-Kit, the gene product of the W locus is a receptor tyrosine kinase that regulates the survival, growth and differentiation of spermatogonial cells (SGCs). Stem cell factor (SCF), the gene product of the steel (Sl) locus is the ligand for c-kit. Normal function of SGCs requires cross-talk between c-kit and SCF through which the receptor-ligand pair regulates the functions of SGCs. The implications of cross-talk between c-kit and SCF in regulating SGC function remains unclear due to the molecular complexity of this interaction. In the present study, we analyzed the interactions between c-kit and SCF in mouse primary SGCs after blocking the c-kit expression by c-kit siRNA and its effect on cell fate were determined using cDNA Expression Array and Real-time PCR. Immunofluorescence (IF) and western blot studies revealed that c-kit protein was detected in SGCs and knocked down to undetectable levels at 24 hr post transfection with 10 nM concentration of c-kit siRNA. We further demonstrated that expression of various genes involved in cell signaling, cell differentiation, apoptosis and cell cycle pathways was altered. SGC functions are affected by SCF signaling through c-kit receptor and this signaling appears to be important to maintain balance between cell proliferation and apoptosis along with the modulation of inflammatory responses of SGCs. To the best of our knowledge, this is the first report that identifies the putative molecular pathways in murine SGCs in response to specific blocking of c-kit-SCF interactions by siRNA. In conclusion, the present study may provide useful insights into siRNA function and hopefully aid in understanding the involvement of c-kit in the early events of SGC activities and spermatogenesis in mice.
Fa u It-tolera nt sca lea ble m U It piggybacking approach on

Indexing terms: Distributed system, Multicast algorithm, Fault tolerance, Logical token ring , Group communication protocol, PeYformance analysis, Virtual token Abstract: A novel reliable, totally ordered multicast protocol on a single logical process ring (called FTSM) is presented. It guarantees totally ordered and atomic delivery of multicast messages in the presence of message loss, site crashes and network partitioning. By placing sequence numbers on messages, a process holding a virtual token multicasts totally ordered messages. Atomic delivery of multicast messages is achieved by piggybacking stable and acknowledged information on the part of both sender and receivers. Virtual token passing and transmission of control messages are piggybacked onto ordered data messages without requiring additional communication overhead. Individual processes handle token passing and control information by applying a local heuristic. FTSM is scaleable because its overhead on achieving total ordering and atomicity does not depend on the size of the process group. Implementation demonstrates that FTSM achieves superior performance over existing protocols in the same hardware setting.
What Is the Impact of mRNA 5′ TL Heterogeneity on Translational Start Site Selection and the Mammalian Cellular Phenotype?

A major determinant in the efficiency of ribosome loading onto mRNAs is the 5′ TL (transcript leader or 5′ UTR). In addition, elements within this region also impact on start site selection demonstrating that it can modulate the protein readout at both quantitative and qualitative levels. With the increasing wealth of data generated by the mining of the mammalian transcriptome, it has become evident that a genes 5′ TL is not homogeneous but actually exhibits significant heterogeneity. This arises due to the utilization of alternative promoters, and is further compounded by significant variability with regards to the precise transcriptional start sites of each (not to mention alternative splicing). Consequently, the transcript for a protein coding gene is not a unique mRNA, but in-fact a complexed quasi-species of variants whose composition may respond to the changing physiological environment of the cell. Here we examine the potential impact of these events with regards to the protein readout.
The Impact of Inadequate Terminal Disinfection on an Outbreak of Imipenem-Resistant Acinetobacter baumannii in an Intensive Care Unit

Background This study was conducted to investigate an outbreak caused by imipenem-resistant Acinetobacter baumannii (IRAB) in a medical intensive care unit (ICU) in a regional hospital. Methods In response to an IRAB outbreak from October 2012 to February 2013, we developed several infection control measures, including an extensive review process of environmental cleaning and disinfection, and used molecular methods to identify each clinical and environmental IRAB isolate. Results During this five-month period, 22 patients were colonized with IRAB and 18 patients had IRAB infections. The in-hospital mortality rate was significantly higher among patients with infections rather than colonizations (44.4% vs 9.1%, p = 0.028). Additionally, nine environmental specimens, including five specimens collected after terminal disinfection, were positive for IRAB. 12 environmental isolates and 28 of 36 available clinical isolates belonged to one unique pulsotype A, which was confirmed by molecular methods. We found the concentration of disinfectant, 0.08% sodium hypochlorite, was inadequate. After correcting the environmental cleansing methods, the surveillance study showed no further IRAB isolates on the control panel surfaces of the medical equipment or in patients in the ICU. Additionally, an in vitro study of IRAB immersed in different concentrations of sodium hypochlorite showed that 0.5% sodium hypochlorite eradicates IRAB after 30 seconds of inoculation, but 0.08% sodium hypochlorite only reduces the bacterial load. Conclusions This study highlights the importance of the preparation of disinfectants to adequately achieve environmental disinfection in the control of IRAB outbreaks in the ICU.
EPS—Then and Now

“Slime” played a brief and spectacular role in the 19th century founded by the theory of primordial slime by Ernst Haeckel. However, that substance was never found and eventually abandoned. Further scientific attention slowly began in the 1930s referring to slime as a microbial product and then was inspired by “How bacteria stick” by Costerton et al. in 1978, and the matrix material was considered to be polysaccharides. Later, it turned out that proteins, nucleic acids and lipids were major other constituents of the extracellular polymeric substances (EPS), an acronym which was highly discussed. The role of the EPS matrix turns out to be fundamental for biofilms, in terms of keeping cells in proximity and allowing for extended interaction, resource capture, mechanical strength and other properties, which emerge from the life of biofilm organisms, including enhanced tolerance to antimicrobials and other stress. The EPS components are extremely complex and dynamic and fulfil many functional roles, turning biofilms into the most ubiquitous and successful form of life on Earth.