948 resultados para Physically Handicapped Persons
Resumo:
A high-fidelity virtual tool for the numerical simulation of low-velocity impact damage in unidirectional composite laminates is proposed. A continuum material model for the simulation of intraply damage phenomena is implemented in a numerical scheme as a user subroutine of the commercially available Abaqus finite element package. Delaminations are simulated using of cohesive surfaces. The use of structured meshes, aligned with fiber directions allows the physically-sound simulation of matrix cracks parallel to fiber directions, and their interaction with the development of delaminations. The implementation of element erosion criteria and the application of intraply and interlaminar friction allow for the simulation of fiber splits and their entanglement, which in turn results in permanent indentation in the impacted laminate. It is shown that this simulation strategy gives sound results for impact energies bellow and above the Barely Visible Impact Damage threshold, up to laminate perforation conditions
Resumo:
Most theodicy responses to the problem of evil have in common the claim that God legitimately allows some evil such that greater good may come. This response is puzzling because the seemingly overwhelming consensus (at least amongst Christian apologists) is that 1) morality is deontological in nature (e.g. our duty of obedience to God’s commands, or acting in accordance with God’s purpose), and 2) relatedly, that humans are made in God’s image (i. e. are rational beings) and thus are worthy of respect. I shall argue that theodicy defenses that claim that God allows some evil such that greater good may come are untenable because they either unnecessarily bifurcate Christian morality in an ad hoc manner, or entail that God cannot have respect for persons.
Resumo:
The Escherichia coli umuDC operon is induced in response to replication-blocking DNA lesions as part of the SOS response. UmuD protein then undergoes an RecA-facilitated self-cleavage reaction that removes its N-terminal 24 residues to yield UmuD′. UmuD′, UmuC, RecA, and some form of the E. coli replicative DNA polymerase, DNA polymerase III holoenzyme, function in translesion synthesis, the potentially mutagenic process of replication over otherwise blocking lesions. Furthermore, it has been proposed that, before cleavage, UmuD together with UmuC acts as a DNA damage checkpoint system that regulates the rate of DNA synthesis in response to DNA damage, thereby allowing time for accurate repair to take place. Here we provide direct evidence that both uncleaved UmuD and UmuD′ interact physically with the catalytic, proofreading, and processivity subunits of the E. coli replicative polymerase. Consistent with our model proposing that uncleaved UmuD and UmuD′ promote different events, UmuD and UmuD′ interact differently with DNA polymerase III: whereas uncleaved UmuD interacts more strongly with β than it does with α, UmuD′ interacts more strongly with α than it does with β. We propose that the protein–protein interactions we have characterized are part of a higher-order regulatory system of replication fork management that controls when the umuDC gene products can gain access to the replication fork.
Resumo:
The yeast Sec1p protein functions in the docking of secretory transport vesicles to the plasma membrane. We previously have cloned two yeast genes encoding syntaxins, SSO1 and SSO2, as suppressors of the temperature-sensitive sec1–1 mutation. We now describe a third suppressor of sec1–1, which we call MSO1. Unlike SSO1 and SSO2, MSO1 is specific for sec1 and does not suppress mutations in any other SEC genes. MSO1 encodes a small hydrophilic protein that is enriched in a microsomal membrane fraction. Cells that lack MSO1 are viable, but they accumulate secretory vesicles in the bud, indicating that the terminal step in secretion is partially impaired. Moreover, loss of MSO1 shows synthetic lethality with mutations in SEC1, SEC2, and SEC4, and other synthetic phenotypes with mutations in several other late-acting SEC genes. We further found that Mso1p interacts with Sec1p both in vitro and in the two-hybrid system. These findings suggest that Mso1p is a component of the secretory vesicle docking complex whose function is closely associated with that of Sec1p.
Resumo:
The herpesvirus entry mediator C (HveC), previously known as poliovirus receptor-related protein 1 (PRR1), and the herpesvirus Ig-like receptor (HIgR) are the bona fide receptors employed by herpes simplex virus-1 and -2 (HSV-1 and -2) for entry into the human cell lines most frequently used in HSV studies. They share an identical ectodomain made of one V and two C2 domains and differ in transmembrane and cytoplasmic regions. Expression of their mRNA in the human nervous system suggests possible usage of these receptors in humans in the path of neuron infection by HSV. Glycoprotein D (gD) is the virion component that mediates HSV-1 entry into cells by interaction with cellular receptors. We report on the identification of the V domain of HIgR/PRR1 as a major functional region in HSV-1 entry by several approaches. First, the epitope recognized by mAb R1.302 to HIgR/PRR1, capable of inhibiting infection, was mapped to the V domain. Second, a soluble form of HIgR/PRR1 consisting of the single V domain competed with cell-bound full-length receptor and blocked virion infectivity. Third, the V domain was sufficient to mediate HSV entry, as an engineered form of PRR1 in which the two C2 domains were deleted and the V domain was retained and fused to its transmembrane and cytoplasmic regions was still able to confer susceptibility, although at reduced efficiency relative to full-length receptor. Consistently, transfer of the V domain of HIgR/PRR1 to a functionally inactive structural homologue generated a chimeric receptor with virus-entry activity. Finally, the single V domain was sufficient for in vitro physical interaction with gD. The in vitro binding was specific as it was competed both by antibodies to the receptor and by a mAb to gD with potent neutralizing activity for HSV-1 infectivity.
Resumo:
Human complement factor H controls spontaneous activation of complement in plasma and appears to play a role in distinguishing host cells from activators of the alternative pathway of complement. In both mice and humans, the protein is composed of 20 homologous short consensus repeat (SCR) domains. The size of the protein suggests that portions of the structure outside the known C3b binding site (SCR 1-4) possess a significant biological role. We have expressed the full-length cDNA of factor H in the baculovirus system and have shown the recombinant protein to be fully active. Mutants of this full-length protein have now been prepared, purified, and examined for cofactor activity and binding to C3b and heparin. The results demonstrate (i) that factor H has at least three sites that bind C3b, (ii) that one of these sites is located in SCR domains 1-4, as has been shown by others, (iii) that a second site exists in the domain 6-10 region, (iv) that a third site resides in the SCR 16-20 region, and (v) that two heparin binding sites exist in factor H, one near SCR 13 and another in the SCR 6-10 region. Functional assays demonstrated that only the first C3b site located in SCR 1-4 expresses factor I cofactor activity. Mutant proteins lacking any one of the three C3b binding sites exhibited 6- to 8-fold reductions in affinity for C3b on sheep erythrocytes, indicating that all three sites contribute to the control of complement activation on erythrocytes. The identification of multiple functionally distinct sites on factor H clarifies many of the heretofore unexplainable behaviors of this protein, including the heterogeneous binding of factor H to surface-bound C3b, the effects of trypsin cleavage, and the differential control of complement activation on activators and nonactivators of the alternative pathway of complement.
Resumo:
We report on a procedure for tissue preparation that combines thoroughly controlled physical and chemical treatments: quick-freezing and freeze-drying followed by fixation with OsO4 vapors and embedding by direct resin infiltration. Specimens of frog cutaneous pectoris muscle thus prepared were analyzed for total calcium using electron spectroscopic imaging/electron energy loss spectroscopy (ESI/EELS) approach. The preservation of the ultrastructure was excellent, with positive K/Na ratios revealed in the fibers by x-ray microanalysis. Clear, high-resolution EELS/ESI calcium signals were recorded from the lumen of terminal cisternae of the sarcoplasmic reticulum but not from longitudinal cisternae, as expected from previous studies carried out with different techniques. In many mitochondria, calcium was below detection whereas in others it was appreciable although at variable level. Within the motor nerve terminals, synaptic vesicles as well as some cisternae of the smooth endoplasmic reticulum yielded positive signals at variance with mitochondria, that were most often below detection. Taken as a whole, the present study reveals the potential of our experimental approach to map with high spatial resolution the total calcium within individual intracellular organelles identified by their established ultrastructure, but only where the element is present at high levels.
Resumo:
The Colloquium on Human-Machine Communication by Voice highlighted the global technical community's focus on the problems and promise of voice-processing technology, particularly, speech recognition and speech synthesis. Clearly, there are many areas in both the research and development of these technologies that can be advanced significantly. However, it is also true that there are many applications of these technologies that are capable of commercialization now. Early successful commercialization of new technology is vital to ensure continuing interest in its development. This paper addresses efforts to commercialize speech technologies in two markets: telecommunications and aids for the handicapped.
Resumo:
Contemporary therapeutic circles utilize the concept of anxiety to describe a variety of disorders. Emotional reductionism is a detriment to the therapeutic community and the persons seeking its help. This dissertation proposes that attention to the emotion of fear clarifies our categorization of particular disorders and challenges emotional reductionism. I propose that the emotion of fear, through its theological relationship to hope, is useful in therapeutic practice for persons who experience trauma and PTSD. I explore the differences between fear and anxiety by deconstructing anxiety. Through this process, I develop four categories which help the emotion of fear stand independent of anxiety in therapy. Temporality, behaviors, antidote and objects are categories which distinguish fear from anxiety. Together, they provide the impetus to explore the emotion of fear. Understanding the emotion of fear requires an examination of its neurophysiological embodiment. This includes the brain structures responsible for fear production, its defensive behaviors and the evolutionary retention of fear. Dual inheritance evolutionary theory posits that we evolved physically and culturally, helping us understand the inescapability of fear and the unique threats humans fear. The threats humans react to develop through subjective interpretations of experience. Sometimes threats, through their presence in our memories and imaginations, inhibit a person's ability to live out a preferred identity and experience hope. Understanding fear as embodied and subjective is important. Process theology provides a religious framework through which fear can be interpreted. In this framework, fear is developed as an adaptive human response. Moreover, fear is useful to the divine-human relationship, revealing an undercurrent of hope. In the context of the divine-human relationship fear is understood as an initial aim which protects a person from a threat, but also preserves them for novel future relationships. Utilizing a "double-listening" stance, a therapist hears the traumatic narrative and counternarratives of resistance and resilience. These counternarratives express an orientation towards hopeful futures wherein persons thrive through living out a preferred identity. A therapeutic practice incorporating the emotion of fear will utilize the themes of survival, coping and thriving to enable persons to place their traumatic narrative within their meaning systems.
Resumo:
This documentary is about the internal displacement of ethnic minorities brought about by politically instigated post-election violence towards ethnic minorities in all eight provinces, namely, Coast, Rift Valley, Western, Eastern, North Eastern, Central Kenya, Nairobi, and Nyanza. During the years of 1991 to 1996, over 15,000 people died and almost 300,000 were displaced in the Rift Valley, Central, Nyanza and Western provinces. Before the 1997 elections, violence erupted. Again, following the disputed presidential elections in December 2007 politically and ethnically instigated displacements resulted in human rights violations against 600,000 people in 8 provinces of Kenya.
Resumo:
An Act of Assembly of Barbadoes to regulate sales at outcry and the proceedings of persons executing the office of Provost Marshall General of the said island and their under officers (leaf 1) ; A state of some matters relative to the office of Provost Marshall, and to the passing of this bill (leaf 9) ; Observations drawn up by Jonathan Blenman Esq. his Majestys Atty. Gen. in Barbadoes ... on the Act as it had been first brought in 1761 (leaf 13) ; and two leaves laid in ; Power of attorney, granted to Christopher Scandrett, signed by Francis Reynolds and his son Thomas (25 April 1766) ; Petition of Francis Reynolds to the Lords Commissioners of Trade and Plantations (1766).