Miracle-dz/UniFAR-FTUs huggingface dataset:
Volumetric, Radiographic, and Histologic Analyses of Demineralized Dentin Matrix Combined with Recombinant Human Bone Morphogenetic Protein-2 for Ridge Preservation: A Prospective Randomized Controlled Trial in Comparison with Xenograft

The aim of this study was to evaluate the clinical, volumetric, radiographic, and histologic aspects of autogenous demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) used for ridge preservation, compared to those of deproteinized bovine bone with collagen (DBBC). Following atraumatic extraction, the socket was filled with DBBC, DDM, or rhBMP-2/DDM. Scanned images of dental casts and cone beam computed tomographs (CBCT) were superimposed for the calculation of soft and hard tissue volume alteration. Preoperative and postoperative measurements of the height and width of the alveolar ridge were compared using CBCT images. After 4 months, bone specimens were harvested for histomorphometric assessment. Loss of hard and soft tissue volume occurred at 4 months after extraction and ridge preservation in all groups. No volumetric differences were detected among the three groups before and 4 months after ridge preservation. The reduction in the horizontal width at 5 mm was higher in the DBBC compared to the DDM. Histologically, approximately 40% newly formed bone was founded in rhBMP-2/DDM group. The autogenous dentin matrix used to fill the socket was as beneficial for ridge preservation as conventional xenografts. The combination of rhBMP-2 with dentin matrix also demonstrated appreciable volumetric stability and higher new bone formation compared to DDM alone and DBBC.
Experiencia y resultados en la aplicación de gestión de requerimientos de software en proyectos a gran escala

Resumen. Desde hace ya algunos años los problemas en la especificación de los requerimientos ha sido un tema común en la industria del software. Para lograr minimizar el impacto de especificar incompleta o incorrectamente los requerimientos han surgido algunas técnicas y herramientas que permiten mitigar este problema. Las metodologías ágiles y los proyectos a gran escala no están ajenos a esta situación. Este trabajo presenta la definición e implementación de mejoras al proceso definido basado en prácticas de ingeniería de requerimientos con el fin de reducir el re-trabajo, proveer reportes objetivos respecto del estado del proyecto, incrementar la frecuencia de entregas del producto para obtener feedback (retroalimentación) y reducir así la cantidad de defectos reportados al final del proyecto, mejorando en consecuencia la satisfacción del cliente.
Bacterial lifestyle shapes the regulation of stringent response activation

Bacteria inhabit enormously diverse niches and have a correspondingly large array of regulatory mechanisms to adapt to often inhospitable and variable environments. The stringent response allows bacteria to quickly reprogram transcription in response to changes in nutrient availability. Although the proteins controlling this response are conserved in almost all bacterial species, recent work has illuminated considerable diversity in the starvation cues and regulatory mechanisms that activate stringent signaling proteins in bacteria from different environments. In this review we describe the signals and genetic circuitries that control the stringent signaling systems of a copiotroph, a bacteriovore, an oligotroph and a mammalian pathogen – Escherichia coli, Myxococcus xanthus, Caulobacter crescentus and Mycobacterium tuberculosis , respectively – and discuss how control of the stringent response in these species is adapted to their particular lifestyles.
PULMONARY, SLEEP, AND CRITICAL CARE UPDATE Update in Lung Cancer 2014

In the past 2 years, lung cancer research and clinical care have advanced signi ﬁ cantly. Advancements in the ﬁ eld have improved outcomes and promise to lead to further reductions in deaths from lung cancer, the leading cause of cancer death worldwide. These advances include identi ﬁ cation of new molecular targets for personalized targeted therapy, validation of molecular signatures of lung cancer risk in smokers, progress in lung tumor immunotherapy, and implementation of population-based lung cancer screening with chest computed tomography in the United States. In this review, we highlight recent research in these areas and challenges for the future.
Does PKM ζ maintain memory?

Work on the long-term stability of memory has identified a potentially critical role for protein kinase Mzeta (PKM ζ ) in maintaining established memory. PKM ζ , an autonomously active isoform of PKC, is hypothesized to sustain those changes that occurred during memory formation in order to preserve the memory engram over time. Initial studies investigating the role of PKM ζ were largely successful in demonstrating a role for the kinase in memory maintenance; disrupting PKM ζ activity with ζ -inhibitory peptide (ZIP) was successful in disrupting a variety of established associations in a number of key brain regions. More recent work, however, has questioned both the role of PKM ζ in memory maintenance and the effectiveness of ZIP as a specific inhibitor of PKM ζ activity. Here, we outline the research both for and against the idea that PKM ζ is a memory maintenance mechanism and discuss how these two lines of research can be reconciled. We conclude by proposing a number of studies that would help to clarify the role of PKM ζ in memory and define other mechanisms the brain may use to maintain memory. a file of an unedited a our we are providing this early version of the The copyediting, typesetting, and review of the resulting proof is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Kinetic Characterizations of Nitrocefin, Cefoxitin, and Meropenem Hydrolysis by β -lactamase from Mycobacterium tuberculosis

The constitutively expressed, chromosomally-encoded β -lactamase (BlaC) is the enzyme responsible for the intrinsic resistance to β -lactam antibiotics in Mycobacterium tuberculosis. Previous studies from this laboratory have shown that the enzyme exhibits an extended-spectrum phenotype, with very high levels of penicillinase and cephalosporinase activity, as well as weak carbapenemase activity (1). In this report, we have determined the pH dependence of the kinetic parameters, revealing that the maximum velocity depends on the ionization state of two groups; a general base exhibiting a pK value of 4.5 and a general acid exhibiting a pK value of 7.8. Having defined a region where the kinetic parameters are pH-independent (pH 6.5), we determined solvent kinetic isotope effects (SKIEs) for three substrates whose k cat values differ by 4.5 orders of magnitude. Nitrocefin is a highly activated, chromogenic cephalosporin derivative that exhibits steady-state solvent kinetic isotope effects of 1.4 on both V and V/K. Cefoxitin is a slower cephalosporin derivative that exhibits a large SKIE on V of 3.9, but a small SKIE of 1.8 on V/K in steady-state experiments. Pre-steady-state, stopped-flow experiments with cefoxitin revealed a burst of β -lactam ring opening with associated SKIE values of 1.6 on the acylation step and 3.4 on the deacylation step. Meropenem is an extremely slow substrate for BlaC, and exhibits burst kinetics in the steady-state experiments. SKIE determinations with meropenem revealed large SKIEs on both the acylation and deacylation step of 3.8 and 4.0, respectively. Proton inventories in all cases were linear, indicating the participation of a single solvent-derived proton in the chemical step responsible for the SKIE. The rate limiting steps for β -lactam hydrolysis of these substrates are analyzed, and the chemical step(s) responsible for the observed SKIE are discussed. we have performed steady state and pre-steady state studies to measure solvent kinetic isotope effects on β -lactams that vary in catalytic efficiency. Cephalosporins, nitrocefin and cefoxitin, are rapidly hydrolyzed by BlaC, whereas the carbapenem meropenem is hydrolyzed extremely slowly. Our comparative kinetic analysis indicates that slow substrates are highly solvent sensitive for both acylation and deacylation reactions, whereas intermediate substrates have a small SKIE on acylation and a larger SKIE on deacylation and the fast substrates exhibit a small SKIE on acylation only. These findings provide greater mechanistic insight into the rate-limiting steps and chemical mechanism of the BlaC-catalyzed hydrolysis of β -lactam substrates.
Kill the Bacteria … and Also Their Messengers?

We consider here a previously neglected aspect of recovery from infectious diseases: how animals dispose of the dead microbes in their tissues. For one of the most important disease-causing microorganisms, Gram-negative bacteria, there is now evidence that the host catabolism of a key microbial molecule is essential for full recovery. As might be expected, it is the same bacterial molecule that animals sense to detect the presence of Gram-negative bacteria in their tissues, the cell wall lipopolysaccharide (LPS). Here, we discuss current knowledge about LPS sensing with emphasis on the host enzyme that inactivates this microbial “messenger” molecule. We also consider the possibility that the rate at which stimulatory microbial molecules undergo inactivation may influence the duration and severity of diseases caused by other infectious agents.
The e(cid:128)ect of Gi-protein inactivation on basal, and b 1 - and b 2 AR-stimulated contraction of myocytes from transgenic mice overexpressing the b 2 -adrenoceptor

1 The atria and ventricles of transgenic mice (TG b 2 ) with cardiac overexpression of the human b 2 - adrenoceptor ( b 2 AR) were initially reported to show maximum contractility in the absence of b -AR stimulation. However, we have previously observed a di(cid:128)erent phenotype in these mice, with myocytes showing normal contractility but reduced b AR responses. We have investigated the roles of cyclic AMP and Gi in basal and b AR function in these myocytes. agonism, the activated cyclic AMP in TG b 2 mice (9.40 + 1.22%, n =8) and was no longer reduced compared to LM mice (8.93 + 1.50%, n =11). Both b 1 - and b 2 AR subtypes were a(cid:128)ected both by the original desensitization and by the resensitization with PTX. 4 PTX treatment has therefore restored the original phenotype, with high basal contractility and little further e(cid:128)ect of isoprenaline. We suggest that both b -AR desensitization and lack of increased basal contraction in ventricular myocytes from our colony of TG b 2 mice were due to increased activity of PTX-sensitive G-proteins. British Journal of (2000) 131, 594–
Antigen-specific TGF- β -induced regulatory T cells but not natural Tregs ameliorate autoimmune arthritis by shifting the balance of Th17 toward Treg cells

Objective— Transferred CD4 + CD25 + Foxp3 + regulatory cells (Tregs) can prevent autoimmune disease, but generally fail to ameliorate established disease. Here we demonstrate that antigen-specific Tregs induced with IL-2 and TGF- β ex-vivo (iTregs), but not equivalent expanded thymus-derived nTregs can prevent progression of established collagen-induced arthritis. Methods— DBA/1 mice with collagen-induced arthritis were treated with iTreg or nTreg generated or expanded in vitro before or shortly after collagen II immunization, and clinical scores were determined. Inflammatory responses were determined by measuring the levels of anti-CII antibody in the serum and histological pathology in joints. The Th1/Th17-mediated autoreactive response was evaluated by determining the cytokine profile of draining lymph node cells by flow cytometry. have more potent protective than polyclonal Tregs the of this to compare the relative effectiveness of collagen expanded, and iTregs induced with and in
THE EXPERT : Vaccinate boys with the HPV vaccine ? Really ?

Tami Thomas and Samuel Snell, Honor Student, respond: The prevalence of human papillomavirus (HPV) infection is increasing in the United States in both low-risk and highrisk groups of men; so, it is imperative that pediatric nurses educate and encourage HPV vaccination for boys (Smith, Gilbert, Melendy, Rana, & Pimenta, 2011). HPV is estimated to currently infect young men 20 years of age and older at rates between 65% and 93% in high-risk populations, and up to 45% among lower risk populations. Despite the usefulness of the vaccine in preventing HPV-related cancers in men, barriers to HPV vaccination still persist (Smith, Gilbert, Melendy, Rana, & Pimenta, 2011). The benefit of the HPV vaccine in boys is often over-looked by the initial focus and marketing of the HPV vaccine as a means to prevent cervical cancer. There is also a lack of knowledge about the virus, such as the fact that more than 130 HPV genotypes exist, and that they are classified as low-risk and high-risk types (Frazer, 2010). Low-risk types (i.e., types 6 and 11) cause genital warts, while high-risk types (i.e., types 16 and 18) can cause cancers of the cervix, anus, oropharynx, penis, vagina, and vulva (Marklund & Hammarstedt, 2011). Current data indicate that HPV infection may be associated with 96–99% of cervical cancers, 90–93% of anal cancers, 12–63% of oropharyngeal cancers, 36–40% of penile cancers, 40% of vaginal cancers, and 40–51% of vulvar cancers (Hernandez et al., 2008; Kroger, Atkinson, Marcuse, & Pickering, 2006; Marklund & Hammarstedt, 2011; Parkin & Bray, 2006; Watson et al., 2008). Vaccinating boys and men ages 9–26 years can prevent more than 5 million cases of
Threshold Switching and Self-Oscillation in Niobium Oxide

Volatile threshold switching, or current controlled negative differential resistance (CC-NDR), has been observed in a range of transition metal oxides. Threshold switching devices exhibit a large non-linear change in electrical conductivity, switching from an insulating to a metallic state under external stimuli. Compact, scalable and low power threshold switching devices are of significant interest for use in existing and emerging technologies, including as a selector element in high-density memory arrays and as solid-state oscillators for hardware-based neuromorphic computing. This thesis explores the threshold switching in amorphous NbOx and the properties of individual and coupled oscillators based on this response. The study begins with an investigation of threshold switching in Pt/NbOx/TiN devices as a function device area, NbOx film thickness and temperature, which provides important insight into the structure of the self-assembled switching region. The devices exhibit combined threshold-memory behaviour after an initial voltage-controlled forming process, but exhibit symmetric threshold switching when the RESET and SET currents are kept below a critical value. In this mode, the threshold and hold voltages are shown to be independent of the device area and film thickness, and the threshold power, while independent of device area, is shown to decrease with increasing film thickness. These results are shown to be consistent with a structure in which the threshold switching volume is confined, both laterally and vertically, to the region between the residual memory filament and the electrode, and where the memory filament has a core-shell structure comprising a metallic core and a semiconducting shell. The veracity of this structure is demonstrated by comparing experimental results with the predictions of a resistor network model, and detailed finite element
High signal-to-noise ratio LDV measurements of pipe flow at low-moderate Reynolds number.

Low Reynolds number velocity flow has been investigated in a horizontal cylindrical duct (internal diameter=0.05 m and length = 6.00 m) by a custom made Laser Doppler Velocimetry system. The LDV facility was based on a 20 mW HeNe laser, some manipulation optics and a novel electro-optic phase modulator for frequency shifting. Because of the low Reynolds number investigated, the noise introduced into the signal by commercial frequency shifters (e.g. Bragg cells) was not acceptable. The new device we have developed is based on a commercially available electro-optic crystal (Pockels cell) constituted by four potassium dihydrogen phosphate KDP ( KD2PO4) of aperture of 3*3 mm. The LDV system has been used to analyse the power spectrum of the velocity fluctuations. An exponential falls off of the spectrum with frequency has been clearly evidenced.
Cross- cultural M4edicine Ethnic Elders and American Health Care-A Physician's Perspective

The aging process is a fugue composed of innumerable themes; the theme of "ethnicity" is by far one of its more dominant. Due to the increasing incidence of chronic, progressive infirmity and acute, catastrophic illness, the elderly are thrust into direct contact with the health care systems of their society. The experiences of ethnic elders in American health care situations are fraught with conflict and mutual dissatisfaction with the physician-patient relationship. Both providers and consumers of health care services harbor differing culture-bound perceptions of health, illness and the healing process; these cultural beliefs define personal and professional needs and expectations and notions of how those needs are to be met by others. Both physicians and patients can enhance their communication and their compassion for one another by acknowledgment of cultural differences and by increased willingness to interpret motives and behavior within native context.
Development, validation and integration of (Q)SAR models to identify androgen active chemicals

Humans are exposed to large numbers of environmental chemicals, some of which potentially interfere with the endocrine system. The identification of potential endocrine disrupting chemicals (EDCs) has gained increasing priority in the assessment of environmental hazards. The U.S. Environmental Protection Agency (U.S. EPA) has developed the Endocrine Disruptor Screening Program (EDSP) which aims to prioritize and screen potential EDCs. The Toxicity Forecaster (ToxCast) program has generated data using in vitro high-throughput screening (HTS) assays measuring activity of chemicals at multiple points along the androgen receptor (AR) activity pathway. In the present study, using a large and diverse data set of 1667 chemicals provided by the U.S. EPA from the combined ToxCast AR assays in the framework of the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA). Two models were built using ADMET Predictor™; one is based on Artificial Neural Networks (ANNs) technology and the other uses a Support Vector Machine (SVM) algorithm; one model is a Decision Tree (DT) developed in R; and two models make use of differently combined sets of structural alerts (SAs) automatically extracted by SARpy. We used two strategies to integrate predictions from single models; one is based on a majority vote approach and the other on prediction convergence. These strategies led to enhanced statistical performance in most cases. Moreover, the majority vote approach improved prediction coverage when one or more single models were not able to provide any estimations. This study integrates multiple in silico approaches as a virtual screening tool for use in risk assessment of endocrine disrupting chemicals.
19 F-NMR Studies on the Acid State of the Intestinal Fatty Acid Binding Protein †

The intestinal fatty acid binding protein (IFABP) is composed of two β -sheets with a large hydrophobic cavity into which ligands bind. After incorporating eight 4- 19 F-phenylalanines into the protein, the acid state of both apo- and holo-IFABP (at pH 2.8 and 2.3) was characterized by means of 1 H-NMR diffusion measurements, circular dichroism and 19 F-NMR. Diffusion measurements show a moderately increased hydrodynamic radius while near and far-UV CD measurements suggest that the acid state has substantial secondary structure as well as persistent tertiary interactions. At pH 2.8, these tertiary interactions have been further characterized by 19 F-NMR, and show an NOE cross peak between residues that are located on different β -strands. Side chain conformational heterogeneity on the millisecond time scale was captured by phase sensitive 19 F- 19 F NOESY. At pH 2.3, native NMR peaks are mostly gone but the protein can still bind fatty acid to form the holo-protein. An exchange cross peak of one phenylalanine in the holo-protein is attributed to increased motional freedom of the fatty acid backbone caused by the slight opening of the binding pocket at pH 2.8. In the acid environment Phe128 and Phe17 show dramatic line broadening and chemical shift changes, reflecting greater degrees of motion around these residues. We propose that there is a separation of specific regions of the protein that gives rise to the larger radius of hydration. Temperature and urea unfolding studies indicate that persistent hydrophobic clusters are native-like and may account for the ability of ligand to bind and induce native-like structure, even at pH 2.3. The acid groups protonated structure. to
A Perfusable 3D Cell–Matrix Tissue Culture Chamber for In Situ Evaluation of Nanoparticle Vehicle Penetration and Transport

A key factor in gene or drug therapy is the development of carriers that can efficiently reach targeted cells from a distal administration. In many gene/drug delivery studies, results obtained in 2D cultures fail to translate to similar results in vivo. In this work, we developed a perfu-sable 3D chamber for studying nanoparticle penetration and transport in cell–gel soft tissue cultures. The compartmented chamber is made of a polydimethylsiloxane (PDMS) top layer with the chamber features, created using micromachined lithography, bonded to a bottom glass coverslip. A solution of cells embedded in a hydrogel is loaded in the chamber between PDMS posts that serve as anchors to the cell–matrix at the gel-media interface. The chamber offers the following unique features: (i) rapid fabrication and simplicity in assembly, (ii) direct in situ cell imaging in a plane normal to the direction of flow or action, (iii) an easily configurable and controllable environment conducive cell culture under static or interstitial flow conditions, and (iv) facile recovery of live cells from chambers for post-experimental analysis. To assess the chamber, we delivered fluorescently labeled nanoparticles of three distinct sizes to cells-embedded Matrigels in the 3D chamber under flow and static conditions. Penetration of nanoparticles were enhanced under interstitial flow while live cell imaging and flow cytometry of recovered cells revealed particle size restrictions to efficient delivery. Although designed for delivery studies, the chamber is versatile and can be easily modified. Thus it may have broad applications for biological, tissue engineering, and therapeutic studies.