Miracle-dz/UniFAR-FTUs huggingface dataset:
Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

BACKGROUND Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. METHODS Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. RESULTS HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. CONCLUSIONS JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.
HPV16‐E6 mRNA is superior to cytokeratin 19 mRNA as a molecular marker for the detection of disseminated tumour cells in sentinel lymph nodes of patients with cervical cancer by quantitative reverse‐transcription PCR

About 10–15% of patients with cervical cancer suffer from recurrence despite histologically negative lymph nodes (pN0). Occult micrometastases or small tumour cell clusters may contribute to disease outcome. The aim of this study was to compare at the RNA level 2 known tumour‐associated genes, HPV16‐E6 and cytokeratin 19 (CK19), as molecular markers for the detection of disseminated tumour cells. Real‐time reverse transcription PCR technology was used to quantify gene expression in histologically positive and negative sentinel lymph nodes (SLN) from 70 patients with cervical cancer. Lymph nodes from noncancer patients were used as controls. Calculated copy numbers were normalised to the geometric average of the most stable housekeeping genes. We observed a good correlation (R = 0.915) between the expression of both markers in SLN with histologically confirmed metastases. However, marker gene expression differed considerably in histologically negative nodes: CK19 transcripts were detected in 90 of 112 SLN (80.4%), whereas only 38 nodes (33.9%) were positive for HPV16 E6 mRNA. In particular, 62 of 74 SLN, which were negative by histology, and HPV16 E6 mRNA expressed CK19 mRNA. Moreover, 8 of 10 lymph nodes from noncancer patients expressed CK19 mRNA. Systematic errors due to RNA degradation or incomplete cDNA could be ruled out. It is concluded that HPV16 E6 mRNA is more specific and more sensitive for the detection of tumour cells in SLN than CK19 mRNA. The specificity of CK19 is limited because of low level expression in uninvolved pelvic lymph nodes. © 2007 Wiley‐Liss, Inc.
Initiation and termination of DNA replication in human rRNA genes

We have used the multicopy human rRNA genes as a model system to study replication initiation and termination in mammalian chromosomes. Enrichment for replicating molecules was achieved by isolating S-phase enriched populations of cells by centrifugal elutriation, purification of DNA associated with the nuclear matrix, and a chromatographic procedure that enriches for molecules containing single-stranded regions, a characteristic of replication forks. Two-dimensional agarose gel electrophoresis techniques were used to demonstrate that replication appears to initiate at multiple sites throughout most of the 31-kb nontranscribed spacer (NTS) of human ribosomal DNA but not within the 13-kb transcription unit or adjacent regulatory elements. Although initiation events were detected throughout the majority of the NTS, some regions may initiate more frequently than others. Termination of replication, the convergence of opposing replication forks, was found throughout the ribosomal DNA repeat units, and, in some repeats, specifically at the junction of the 3' end of the transcription unit and the NTS. This site-specific termination of replication is the result of pausing of replication forks near the sites of transcription termination. The naturally occurring multicopy rRNA gene family offers a unique system to study mammalian DNA replication without the use of chemical synchronization agents.
A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases.

OBJECTIVE Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a severe, early-onset autoinflammatory disease characterized by an urticaria-like rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease-causing mutations in only approximately 55-60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID. METHODS Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed. RESULTS The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria-like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in approximately 30-38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease-causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells. CONCLUSION Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease-causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin-associated periodic syndrome.
Detailed Structural-Functional Analysis of the Krüppel-like Factor 16 (KLF16) Transcription Factor Reveals Novel Mechanisms for Silencing Sp/KLF Sites Involved in Metabolism and Endocrinology

Background: KLF16 is the least characterized family member of recently described metabolic regulators. Results: We extensively characterize mechanisms of DNA binding and chromatin coupling used by KLF16 to regulate metabolic gene expression. Conclusion: KLF16 is a novel regulator of metabolic genes by regulatable coupling to Sin3-histone deacetylase complexes. Significance: This knowledge reveals key mechanisms used by KLF16 as a regulator of metabolic gene expression. Krüppel-like factor (KLF) proteins have elicited significant attention due to their emerging key role in metabolic and endocrine diseases. Here, we extend this knowledge through the biochemical characterization of KLF16, unveiling novel mechanisms regulating expression of genes involved in reproductive endocrinology. We found that KLF16 selectively binds three distinct KLF-binding sites (GC, CA, and BTE boxes). KLF16 also regulated the expression of several genes essential for metabolic and endocrine processes in sex steroid-sensitive uterine cells. Mechanistically, we determined that KLF16 possesses an activation domain that couples to histone acetyltransferase-mediated pathways, as well as a repression domain that interacts with the histone deacetylase chromatin-remodeling system via all three Sin3 isoforms, suggesting a higher level of plasticity in chromatin cofactor selection. Molecular modeling combined with molecular dynamic simulations of the Sin3a-KLF16 complex revealed important insights into how this interaction occurs at an atomic resolution level, predicting that phosphorylation of Tyr-10 may modulate KLF16 function. Phosphorylation of KLF16 was confirmed by in vivo 32P incorporation and controlled by a Y10F site-directed mutant. Inhibition of Src-type tyrosine kinase signaling as well as the nonphosphorylatable Y10F mutation disrupted KLF16-mediated gene silencing, demonstrating that its function is regulatable rather than constitutive. Subcellular localization studies revealed that signal-induced nuclear translocation and euchromatic compartmentalization constitute an additional mechanism for regulating KLF16 function. Thus, this study lends insights on key biochemical mechanisms for regulating KLF sites involved in reproductive biology. These data also contribute to the new functional information that is applicable to understanding KLF16 and other highly related KLF proteins.
A novel deep learning approach for classification of EEG motor imagery signals

Objective. Signal classification is an important issue in brain computer interface (BCI) systems. Deep learning approaches have been used successfully in many recent studies to learn features and classify different types of data. However, the number of studies that employ these approaches on BCI applications is very limited. In this study we aim to use deep learning methods to improve classification performance of EEG motor imagery signals. Approach. In this study we investigate convolutional neural networks (CNN) and stacked autoencoders (SAE) to classify EEG Motor Imagery signals. A new form of input is introduced to combine time, frequency and location information extracted from EEG signal and it is used in CNN having one 1D convolutional and one max-pooling layers. We also proposed a new deep network by combining CNN and SAE. In this network, the features that are extracted in CNN are classified through the deep network SAE. Main results. The classification performance obtained by the proposed method on BCI competition IV dataset 2b in terms of kappa value is 0.547. Our approach yields 9% improvement over the winner algorithm of the competition. Significance. Our results show that deep learning methods provide better classification performance compared to other state of art approaches. These methods can be applied successfully to BCI systems where the amount of data is large due to daily recording.
Do Phytotropins Inhibit Auxin Efflux by Impairing Vesicle Traffic?1

Phytotropins such as 1-N-naphthylphthalamic acid (NPA) strongly inhibit auxin efflux, but the mechanism of this inhibition remains unknown. Auxin efflux is also strongly decreased by the vesicle trafficking inhibitor brefeldin A (BFA). Using suspension-cultured interphase cells of the BY-2 tobacco (Nicotiana tabacum L. cv Bright-Yellow 2) cell line, we compared the effects of NPA and BFA on auxin accumulation and on the arrangement of the cytoskeleton and endoplasmic reticulum (ER). The inhibition of auxin efflux (stimulation of net accumulation) by both NPA and BFA occurred rapidly with no measurable lag. NPA had no observable effect on the arrangement of microtubules, actin filaments, or ER. Thus, its inhibitory effect on auxin efflux was not mediated by perturbation of the cytoskeletal system and ER. BFA, however, caused substantial alterations to the arrangement of actin filaments and ER, including a characteristic accumulation of actin in the perinuclear cytoplasm. Even at saturating concentrations, NPA inhibited net auxin efflux far more effectively than did BFA. Therefore, a proportion of the NPA-sensitive auxin efflux carriers may be protected from the action of BFA. Maximum inhibition of auxin efflux occurred at concentrations of NPA substantially below those previously reported to be necessary to perturb vesicle trafficking. We found no evidence to support recent suggestions that the action of auxin transport inhibitors is mediated by a general inhibition of vesicle-mediated protein traffic to the plasma membrane.
Characteristics and Outcomes of Serious Traumatic Injury in Older Adults

OBJECTIVES: To describe the seriously injured older adult; characterize and compare the differences in injury characteristics and outcomes in three subgroups of seriously injured older adults: aged 65 to 74, 75 to 84, and 85 and older; and identify risk factors for death, complications, and discharge placement at hospital discharge.
A Piezoelectric-Driven Three-Dimensional MEMS VOA Using Attenuation Mechanism With Combination of Rotational and Translational Effects

A gold-coated silicon mirror (5 mm 5 mm) actuated by piezoelectric (PZT) cantilever beams has been investigated for variable optical attenuator applications. The device is micromachined from a SOI substrate with a 5 μm thick Si device layer, with multilayers of Pt/Ti/PZT/Pt/Ti deposited as electrode materials. A large Si mirror plate and 110 arrayed PZT cantilevers arranged in parallel are formed after the release process. The ten cantilevers are designed to be electrically isolated from one another. A dual-core fiber collimator is aligned perpendicularly to the mirror in a 3-D light attenuation arrangement. Thus, three modes of attenuation mechanisms were investigated based on rotational and translational effects. A dynamic attenuation range of 40 dB is achieved at 1 V and 1.8 V for bending and torsional mode, respectively.
Managed care organizational characteristics and health care use among children with special health care needs.

OBJECTIVE To examine the relationship between features of managed care organizations (MCOs) and health care use patterns by children. DATA SOURCES Telephone survey data from 2,223 parents of children with special health care needs, MCO-administrator interview data, and health care claims data. STUDY DESIGN Cross-sectional survey data from families about the number of consequences of their children's conditions and from MCO administrators about their plans' organizational features were used. Indices reflecting the MCO characteristics were developed using data reduction techniques. Hierarchical models were developed to examine the relationship between child sociodemographic and health characteristics and the MCO indices labeled: Pediatrician Focused (PF) Index, Specialist Focused (SF) Index, and Fee for Service (FFS) Index, and outpatient use rates and charges, inpatient admissions, emergency room (ER) visits, and specialty consultations. DATA COLLECTION/EXTRACTION METHODS The telephone and MCO-administrator survey data were linked to the enrollment and claims files. PRINCIPAL FINDINGS The child's age, gender, and condition consequences were consistent predictor variables related to health care use and charges. The PF Index was associated with decreased outpatient use rates and charges and decreased inpatient admissions. The SF Index was associated with increased ER visits and decreased specialty consultations, while the FFS Index was associated with increased outpatient use rates and charges. CONCLUSION After controlling for sociodemographic and health characteristics, the PF, SF, and FFS indices were significantly associated with children's health care use patterns.
Facial Expression Recognition Utilizing Local Direction-Based Robust Features and Deep Belief Network

Emotional health plays very vital role to improve people’s quality of lives, especially for the elderly. Negative emotional states can lead to social or mental health problems. To cope with emotional health problems caused by negative emotions in daily life, we propose efficient facial expression recognition system to contribute in emotional healthcare system. Thus, facial expressions play a key role in our daily communications, and recent years have witnessed a great amount of research works for reliable facial expressions recognition (FER) systems. Therefore, facial expression evaluation or analysis from video information is very challenging and its accuracy depends on the extraction of robust features. In this paper, a unique feature extraction method is presented to extract distinguished features from the human face. For person independent expression recognition, depth video data is used as input to the system where in each frame, pixel intensities are distributed based on the distances to the camera. A novel robust feature extraction process is applied in this work which is named as local directional position pattern (LDPP). In LDPP, after extracting local directional strengths for each pixel such as applied in typical local directional pattern (LDP), top directional strength positions are considered in binary along with their strength sign bits. Considering top directional strength positions with strength signs in LDPP can differentiate edge pixels with bright as well as dark regions on their opposite sides by generating different patterns whereas typical LDP only considers directions representing the top strengths irrespective of their signs as well as position orders (i.e., directions with top strengths represent 1 and rest of them 0), which can generate the same patterns in this regard sometimes. Hence, LDP fails to distinguish edge pixels with opposite bright and dark regions in some cases which can be overcome by LDPP. Moreover, the LDPP capabilities are extended through principal component analysis (PCA) and generalized discriminant analysis (GDA) for better face characteristic illustration in expression. The proposed features are finally applied with deep belief network (DBN) for expression training and recognition.
Multiple capillary DNA sequencer that uses fiber‐optic illumination and detection

An 8‐capillary prototype electrophoresis system for DNA sequencing has been construted. The sequence of 400–450 bases can be obtained from each capillary in less than an hour form sequencing reactions generated with four‐color fluorescent terminators. Illumination of each capillary and collection of fluorescence is through individual optical fibers. Resolution of the DNA ladder is through a replaceable sieving matrix of linear polyacrylamide in reusable coated capillaries. Light from an argon ion laser is introduced into a fused biconically tapered fiber‐optic splitter, and individual fibers deliver approximately 10 mW of 514 nm light to each of the eight electrophoresis capillaries. Illumination and collection are by fibers normal to the surface of the electrophoresis capillary and at right angle to each other. Illumination by a fiber with low numerical aperture and collection by a fiber with high numerical aperture provides good sensitivity and signal‐to‐noise ratios without the need for microlenses (limit of detection: 1.5 × 10−11 M fluorescein analog dye with a signal‐to‐noise ratio of 2). The eight collection fibers are passed in parallel through holographic filters for Rayleigh rejection and into an imaging spectrograph, which simultaneously displays the full fluorsecence spectrum (475–648 nm) from the eight capillaries in parallel on the surface of an intensified chargecoupled device (CCD). The CCD is read out at a rate of 3.4 complete images per second.
Assessment of agitation in elderly patients with dementia: correlations between informant rating and direct observation

Assessment of behavior problems in elderly persons with dementia is important for understanding and managing those behaviors. The most common method for assessing agitation is the use of informant ratings; however, these ratings may be affected by staff bias, inaccurate or insufficient memory, or stress. An alternative method is direct observation, which is more objective, but very costly and necessitates time sampling, thereby limiting the period covered by the assessment. To date, little research attention has been given to the degree to which these two methods converge.
Proteomic pattern changes associated with obesity‐induced asthenozoospermia

Obesity, an increasingly frequent societal disease can also be accompanied by declines in spermatozoa quality and male subfecundity. To determine if there are obesity‐associated proteomic changes potentially affecting sperm quality and motility, differential proteomic analysis was performed on spermatozoa from both obesity‐associated asthenozoospermia and clinically healthy individuals, using a label‐free quantitative LC‐MS/MS approach. We resolved 1975 proteins in the human sperm proteome, amongst which, 105 proteins were less abundant, whereas 22 other proteins increased in obesity‐associated asthenozoospermia. Functional category analyses indicated that the differentially expressed proteins are mainly related to cytoskeletal regulation, vesicle biogenesis, metabolism, and protein degradation involved in spermiogenesis and sperm motility. Furthermore, declines in endoplasmic reticulum protein 57 (ERp57) and actin‐binding‐related protein T2 (ACTRT2) expression were verified by immunofluorescence, Western blot, and flow cytometry analyses. It is evident that ERp57 is localized in the acrosome region, neck and principal piece of human spermatozoa, whereas ACTRT2 is localized in the post‐acrosomal region and middle piece. Thus, these differences in protein expression in asthenozoospermia may contribute to the underlying sperm quality defects afflicting these individuals. Notably, declines in ERp57 and ACTRT2 expression in obesity‐associated asthenozoospermia may play critical roles in reducing sperm motility.
Soft sensor based on generalized support vector machines for microbiological fermentation

Microbiological fermentation is a kind of complicated batch process that is severely nonlinear and time variant. There are many process parameters need to monitor and control in order to make the microbiological fermentation process successful. So it is important to measure the process variables. But the instrumentation and sensors available for fermentation control do not cover all the desirable or necessary measurements. In fermentation processes, many important internal variables can't be measured. Soft sensor has become an indispensable method to measure internal variables in fermentation processes. In this paper, we propose a new method of soft sensor constructed with generalized support vector machine for microbiological fermentation. We discuss how to construct soft sensor with generalized support vector machine and least square generalized support vector machine respectively. This method was compared with neural network in the experiment of soft sensor construction. Experiment results demonstrate this method of constructing soft sensor in microbiological fermentation is very valid.