Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in the Carboxyl-Terminal Domain of the Small Hepatitis B Virus Envelope Protein Impair the Assembly of Hepatitis Delta Virus Particles

ABSTRACT The carboxyl-terminal domain of the small (S) envelope protein of hepatitis B virus was subjected to mutagenesis to identify sequences important for the envelopment of the nucleocapsid during morphogenesis of hepatitis delta virus (HDV) virions. The mutations consisted of carboxyl-terminal truncations of 4 to 64 amino acid residues and small combined deletions and insertions spanning the entire hydrophobic domain between residues 163 and 224. Truncation of as few as 14 residues partially inhibited glycosylation and secretion of S and prevented assembly or stability of HDV virions. Short internal combined deletions and insertions were tolerated for secretion of subviral particles with the exceptions of those affecting residues 164 to 173 and 219 to 223. However, mutants competent for subviral particle secretion had a reduced capacity for HDV assembly compared to that of the wild type. One exception was a mutant carrying a deletion of residues 214 to 218, which exhibited a twofold increase in HDV assembly (or stability), whereas deletions of residues 179 to 183, 194 to 198, and 199 to 203 were the most inhibitory. Substitutions of single amino acids between residues 194 and 198 demonstrated that HDV assembly deficiency could be assigned to the replacement of the tryptophan residue at position 196. We concluded that assembly of stable HDV particles requires a specific function of the carboxyl terminus of S which is mediated at least in part by Trp-196.
Injury, Interiority, and Isolation in Men’s Suicidality

Men’s high suicide rates have been linked to individual risk factors including history of being abused as a child, single marital status, and financial difficulties. While it has also been suggested that the normative influences of hegemonic masculinities are implicated in men’s suicide, the gendered experiences of male suicidality are poorly understood. In the current photovoice study, 20 men who previously had suicidal thoughts, plans, and/or attempts were interviewed as a means to better understanding the connections between masculinities and their experiences of suicidality. The study findings revealed injury, interiority, and isolation as interconnected themes characterizing men’s suicidality. Injury comprised an array of childhood and/or cumulative traumas that fueled men’s ruminating thoughts inhibiting recovery and limiting hopes for improved life quality. In attempting to blunt these traumas, many men described self-injuring through the overuse of alcohol and other drugs. The interiority theme revealed how suicidal thoughts can fuel hopelessness amid summonsing remedies from within. The challenges to self-manage, especially when experiencing muddled thinking and negative thought were evident, and led some participants to summons exterior resources to counter suicidality. Isolation included separateness from others, and was linked to abandonment issues and not having a job and/or partner. Self-isolating also featured as a protection strategy to avoid troubling others and/or reducing exposure to additional noxious stimuli. The study findings suggest multiple intervention points and strategies, the majority of which are premised on promoting men’s social connectedness. The destigmatizing value of photovoice methods is also discussed.
Providing a medical home: the cost of care coordination services in a community-based, general pediatric practice.

OBJECTIVE To determine the cost of unreimbursable care coordination services for children with special health care needs (CSHCN) in 1 community-based, general pediatric practice. METHODS A measurement tool was developed to quantify the precise activities involved in providing comprehensive, coordinated care for CSHCN. Costs of providing this care were calculated on the basis of time spent multiplied by the average salary of the office personnel performing the care coordination service. In addition, data were collected regarding the complexity level of the patient requiring the service, the type of service provided, and the outcome. RESULTS During the 95-day study period, 774 encounters that led to care coordination activities were logged, representing service provision to 444 separate patients. When these encounters were examined on the basis of clinical complexity of the patient, the most complex patients constituted 11% of the population of CSHCN yet accounted for 25% of the encounters. In addition, care coordination activities for these clinically complex CSHCN engaged office staff 4 times as long when compared with less clinically complex CSHCN. Overall, 51% of the encounters were attributable to coordinating care for problems not considered typically medical and included activities such as processing referrals with managed care organizations, consulting with schools or other educational programs, and providing oversight for psychosocial issues. On the basis of national salary and benefits data, the annual cost of the time spent coordinating care for CSHCN in this medical home model ranged from 22,809 dollars to 33,048 dollars (representing the 25th and 75th percentiles, respectively). CONCLUSIONS The costs of providing care coordination services to CSHCN in a medical home are appreciable but not prohibitive. Standardization of care coordination practices is essential because it makes the medical home more amenable to quality improvement interventions. Mechanisms to finance unreimbursable care coordination activities must be developed to achieve the Healthy People 2010 objective that all CSHCN have access to a medical home.
Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children.

BACKGROUND Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea. OBJECTIVES To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children. PATIENTS AND METHODS From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5. RESULTS We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients. CONCLUSION Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit.
Junior: The Stanford entry in the Urban Challenge

This article presents the architecture of Junior, a robotic vehicle capable of navigating urban environments autonomously. In doing so, the vehicle is able to select its own routes, perceive and interact with other traffic, and execute various urban driving skills including lane changes, U‐turns, parking, and merging into moving traffic. The vehicle successfully finished and won second place in the DARPA Urban Challenge, a robot competition organized by the U.S. Government. © 2008 Wiley Periodicals, Inc.
Absence of Thiol-Disulfide Oxidoreductase DsbA Impairs cbb3-Type Cytochrome c Oxidase Biogenesis in Rhodobacter capsulatus

The thiol-disulfide oxidoreductase DsbA carries out oxidative folding of extra-cytoplasmic proteins by catalyzing the formation of intramolecular disulfide bonds. It has an important role in various cellular functions, including cell division. The purple non-sulfur bacterium Rhodobacter capsulatus mutants lacking DsbA show severe temperature-sensitive and medium-dependent respiratory growth defects. In the presence of oxygen, at normal growth temperature (35°C), DsbA− mutants form colonies on minimal medium, but they do not grow on enriched medium where cells elongate and lyse. At lower temperatures (i.e., 25°C), cells lacking DsbA grow normally in both minimum and enriched media, however, they do not produce the cbb3-type cytochrome c oxidase (cbb3-Cox) on enriched medium. Availability of chemical oxidants (e.g., Cu2+ or a mixture of cysteine and cystine) in the medium becomes critical for growth and cbb3-Cox production in the absence of DsbA. Indeed, addition of Cu2+ to the enriched medium suppresses, and conversely, omission of Cu2+ from the minimal medium induces, growth and cbb3-Cox defects. Alleviation of these defects by addition of redox-active chemicals indicates that absence of DsbA perturbs cellular redox homeostasis required for the production of an active cbb3-Cox, especially in enriched medium where bioavailable Cu2+ is scarce. This is the first report describing that DsbA activity is required for full respiratory capability of R. capsulatus, and in particular, for proper biogenesis of its cbb3-Cox. We propose that absence of DsbA, besides impairing the maturation of the c-type cytochrome subunits, also affects the incorporation of Cu into the catalytic subunit of cbb3-Cox. Defective high affinity Cu acquisition pathway, which includes the MFS-type Cu importer CcoA, and lower production of the c-type cytochrome subunits lead together to improper assembly and degradation of cbb3-Cox.
β2-spectrin depletion impairs DNA damage repair

β2-Spectrin (β2SP/SPTBN1, gene SPTBN1) is a key TGF-β/SMAD3/4 adaptor and transcriptional cofactor that regulates TGF-β signaling and can contribute to liver cancer development. Here we report that cells deficient in β2-Spectrin (β2SP) are moderately sensitive to ionizing radiation (IR) and extremely sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with IR or ICL agents (formaldehyde, cisplatin, camptothecin, mitomycin), β2SP deficient cells displayed a higher frequency of cells with delayed γ-H2AX removal and a higher frequency of residual chromosome aberrations. Following hydroxyurea (HU)-induced replication stress, β2SP-deficient cells displayed delayed disappearance of γ-H2AX foci along with defective repair factor recruitment (MRE11, CtIP, RAD51, RPA, and FANCD2) as well as defective restart of stalled replication forks. Repair factor recruitment is a prerequisite for initiation of DNA damage repair by the homologous recombination (HR) pathway, which was also defective in β2SP deficient cells. We propose that β2SP is required for maintaining genomic stability following replication fork stalling, whether induced by either ICL damage or replicative stress, by facilitating fork regression as well as DNA damage repair by homologous recombination.
Melatonin synergistically enhances cisplatin‐induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK‐OV‐3 cells

Abstract: To evaluate melatonin’s ability to enhance ovarian cancer cells to cisplatin treatment for ovarian cancer, this study was performed. Melatonin by itself had no significant cytotoxicity against SK‐OV‐3 cells, while cisplatin suppressed the cell viability in a dose‐dependent manner. Combined treatment with cisplatin and melatonin synergistically inhibited the viability of SK‐OV‐3 cells with the synergism between two drugs (1 > combination index). In contrast, melatonin revealed the protective effect against cisplatin‐induced cytotoxicity in OSEN normal ovarian epithelial cells. Cotreatment with cisplatin and melatonin increased the sub‐G1 DNA contents and TdT‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells compared with cisplatin control in SK‐OV‐3 cells, suggesting that melatonin augments cisplatin‐induced apoptosis. Consistently, combined treatment of cisplatin and melatonin increased the cleavage of caspase‐3 and poly‐(ADP‐ribose) polymerase (PARP). Importantly, melatonin synergistically inhibited the phosphorylation of extracellular signal–regulated kinase (ERK) along with dephosphorylation of 90‐kDa ribosomal S6 kinase (p90RSK) and heat shock protein 27 (HSP27) induced by cisplatin. Furthermore, melatonin remarkably blocked the expression and colocalization of p90RSK and HSP27 by combination treatment with cisplatin. Taken together, our findings demonstrate that melatonin enhances cisplatin‐induced apoptosis via the inactivation of ERK/p90RSK/HSP27 cascade in SK‐OV‐3 cells as a potent synergist to cisplatin treatment.
Simulation and feedback control of the Ahmed body flow exhibiting symmetry breaking behaviour

The present work considers the low-Reynolds-number wake flow behind a squareback Ahmed body, in close proximity to a ground. At low Reynolds numbers such wakes are known to undergo a series of bifurcations to a state that breaks reflectional symmetry. The symmetry breaking of the wake also persists at turbulent high Reynolds numbers, where it manifests as bi-modal behaviour with random switching between the asymmetric states. Thus far, it has only been possible to study the low-Reynolds-number sequence of bifurcations experimentally and mathematically. The present work presents the first numerical simulations capturing the sequence of symmetry breaking bifurcations that occur. A study of how the wake topology changes throughout suggests that interaction between the closer top/bottom pair of parallel shear layers can only dominate once there is sufficient underbody flow. When this occurs, the two main vortex structures in the wake switch from being horizontally to vertically aligned. A linear feedback control strategy, designed to attenuate base pressure force fluctuations, is then implemented. This causes an accompanying reduction in drag and re-symmetrisation of the wake. Analysis using the dynamic mode decomposition confirms that the wake shedding mode is re-symmetrised. This work motivates future attempts to capture wake symmetry breaking and bi-modality in numerical simulations, and application of a promising feedback control strategy at higher, turbulent Reynolds numbers.
Live or let die: posttranscriptional gene regulation in cell stress and cell death

Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse stresses shut down most protein translation to conserve energy and lead to rapid remodeling of the proteome to promote repair. Pre‐mRNA splicing and mRNA stability are fundamentally altered under some stress conditions. Stress pathways coordinate a cytoprotective repair response, while simultaneously initiating signaling that can ultimately trigger cell death. How the cell mediates the decision between repair and apoptosis is largely not understood. In some stresses, microRNAs may tip the balance. Here, we review what is known about posttranscriptional gene regulation during stress, focusing on what is still unknown and how new technologies might be used to understand what changes are most physiologically important in different forms of stress and death.
Proinflammatory cytokines induce RANTES and MCP-1 synthesis in human corneal keratocytes but not in corneal epithelial cells. Beta-chemokine synthesis in corneal cells.

PURPOSE To determine whether human corneal epithelial cells and keratocytes produce chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) protein and monocyte chemotactic protein-1 (MCP-1) after exposure to proinflammatory cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha). METHODS Pure cultures of human corneal epithelial cells and keratocytes were exposed to increasing concentrations of either human recombinant IL-1 alpha or TNF-alpha. At selected time intervals after exposure, culture supernatants were removed and assayed for RANTES and MCP-1 by the enzyme-linked immunosorbent assay. Total RNA was extracted from the cell cultures, and steady state mRNA levels were measured by reverse transcriptase-polymerase chain reaction. RESULTS Exposure to keratocytes to either IL-1 alpha or TNF-alpha resulted in > 100-fold increases in RANTES protein secretion and > 150-fold increases in MCP-1 protein secretion, as well as in rapid sustained increases in intracellular levels of their corresponding mRNAs. Exposure of corneal epithelial cells to IL-1 alpha and TNF-alpha did not stimulate MCP-1 secretion nor intracellular levels of MCP-1 mRNA. Epithelial cells also failed to secrete RANTES protein even through the two inducing cytokines did stimulate increased expression of RANTES mRNA. CONCLUSIONS These results suggest that RANTES and MCP-1 gene expression in human keratocytes differs markedly from their expression in human corneal epithelial cells and that the stroma of the cornea may be more important than the epithelium in recruitment of mononuclear leukocytes responsible for cell-mediated immunity.
The bridge test for sampling narrow passages with probabilistic roadmap planners

Probabilistic roadmap (PRM) planners have been successful in path planning of robots with many degrees of freedom, but narrow passages in a robot's configuration space create significant difficulty for PRM planners. This paper presents a hybrid sampling strategy in the PRM framework for finding paths through narrow passages. A key ingredient of the new strategy is the bridge test, which boosts the sampling density inside narrow passages. The bridge test relies on simple tests of local geometry and can be implemented efficiently in high-dimensional configuration spaces. The strengths of the bridge test and uniform sampling complement each other naturally and are combined to generate the final hybrid sampling strategy. Our planner was tested on point robots and articulated robots in planar workspaces. Preliminary experiments show that the hybrid sampling strategy enables relatively small roadmaps to reliably capture the connectivity of configuration spaces with difficult narrow passages.
Syndication in private equity industry: comparing the strategies of independent and captive venture capitalists

This paper aims to connect two strands of the venture capital literature: the inter-relationships among venture capitalists (VCs) on the one hand, and between VCs and their funds providers on the other hand. It examines the existence of a relationship between type of fund provider and skill characteristics of the VCs partners in a syndication deal. In other words, it examines whether captive/independent VCs privilege partnerships with firms with specific skills? We develop a theoretical analysis to compare the syndication behaviors of independent and captive VCs. Based on a game-theoretical approach, we model whether the type of lead VC has an influence on the optimal (related to skill levels) partnerships established with syndicate members. Our paper highlights that the source of finance matters for the syndication choice. Its influence takes two forms. The first is related to the heterogeneity between a captive and an independent VC in relation to the returns from the funded project: independent VCs (IVCs) tend to participate in higher profitability syndicated funding projects than captive VCs (CVCs). The second is related to heterogeneity among captive and independent VCs in the ability to syndicate. This is related strongly to the types of financial incentives funds providers employ to align the VC's interests with their own goals. Our analysis suggests that these incentives play a decisive role in the bargaining power of the lead VC and generally make IVCs more attractive syndication partners for other venture capitalists.
Body perception and meal type across age and gender on a Mediterranean island (Sardinia)

Abstract Our aim was to describe the differences in consumption of types of meal (complete/incomplete) eaten at lunch and dinner by gender in people of different age groups (children, young adults and seniors). In particular, we wanted to investigate the differences in choice of meal based on perceived weight. The study involved 516 participants, of which 156 were children (8-12y), 187 were young adults (19-30y) and 173 were elderly (65-90y). A cross-sectional analysis was carried out into the choice of meal type based on the different age groups and genders, on the three Body Mass Index categories (under, normal, overweight), on the three levels of self-perception (slim, normal and heavy) and on the degrees of perception of one’s body weight (underestimation, accurate estimation, overestimation). The food eaten was grouped into three types of daily meal: (a) incomplete, (b) complete lunch or dinner, (c) always complete. Differences emerged in the type of meal eaten according to age, gender and perceived weight. The results show gender differences in associations with meal type according to the way in which body mass is measured or perceived. The choice of complete/incomplete meal type changes according to whether real weight or perceived weight is considered.
Non-linear matrix factorization with Gaussian processes

A popular approach to collaborative filtering is matrix factorization. In this paper we develop a non-linear probabilistic matrix factorization using Gaussian process latent variable models. We use stochastic gradient descent (SGD) to optimize the model. SGD allows us to apply Gaussian processes to data sets with millions of observations without approximate methods. We apply our approach to benchmark movie recommender data sets. The results show better than previous state-of-the-art performance.