Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage

The role of delayed hypersensitivity in the pathogenesis of Chlamydia t trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayed-type hypersensitivity reaction was observed, characterized by mononuclear cell infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study showed that C. trachomatis infection in monkeys induced delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma.     

Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria

Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention.     

Bioinspired Nacre‐Like Ceramic with Nickel Inclusions Fabricated by Electroless Plating and Spark Plasma Sintering

Hybrid composites of layered brittle‐ductile constituents assembled in a brick‐and‐mortar architecture are promising for applications requiring high strength and toughness. Mostly, polymer mortars have been considered as the ductile layer in brick‐and‐mortar composites. However, low stiffness of polymers does not efficiently transfer the shear between hard ceramic bricks. Theoretical models point to metals as a more efficient mortar layer. However, infiltration of metals into ceramic scaffold is non‐trivial, given the low wetting between metals and ceramics. The authors report on an alternative approach to fabricate brick‐and‐mortar ceramic‐metal composites by using electroless plating of nickel (Ni) on alumina micro‐platelets, in which Ni‐coated micro‐platelets are subsequently aligned by a magnetic field, taking advantage of ferromagnetic properties of Ni. The assembled Ni‐coated ceramic scaffold is then sintered using spark plasma sintering (SPS) to locally create Ni mortar layers between ceramic platelets, as well as to sinter the ceramic micro‐platelets. The authors report on materials and mechanical properties of the fabricated composite. The results show that this approach is promising toward development of bioinspired ceramic‐metal composites.

     

Co-capping studies reveal CD8/TCR interactions after capping CD8 beta polypeptides and intracellular associations of CD8 with p56(lck)

A reaction-diffusion model was developed to predict the fate of nitric oxide (NO) released by cells of the immune system. The model was used to analyze data obtained previously using macrophages attached to microcarrier beads suspended in a stirred vessel. Activated macrophages synthesize NO, which is oxidized in the culture medium by molecular oxygen and superoxide (O2-, also released by the cells), yielding mainly nitrite (NO2-) and nitrate (NO3-) as the respective end products. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations adjacent to a representative carrier bead and a well-mixed bulk solution. It was found that the concentration of NO was relatively uniform in the film. In contrast, essentially all of the O2- was calculated to be consumed within approximately 2 microm of the cell surfaces, due to its reaction with NO to yield peroxynitrite. The decomposition of peroxynitrite caused its concentration to fall to nearly zero over a distance of approximately 30 microm from the cells. Although the film regions (which had an effective thickness of 63 microm) comprised just 2% of the reactor volume and were predicted to account for only 6% of the NO2- formation under control conditions, they were calculated to be responsible for 99% of the NO3- formation. Superoxide dismutase in the medium (at 3.2 microM) was predicted to lower the ratio of NO3- to NO2- formation rates from near unity to <0.5, in reasonable agreement with the data. The NO3-/NO2- ratio was predicted to vary exponentially with the ratio of O2- to NO release rates from the cells. Recently reported reactions involving CO2 and bicarbonate were found to have important effects on the concentrations of peroxynitrite and nitrous anhydride, two of the compounds that have been implicated in NO cytotoxicity and mutagenesis.     

Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence

Surgical treatment of refractory epilepsy in childhood and adolescence has been shown to be effective in reducing the seizure frequency. This paper examines the question: "Does this result in a better socioeconomic outcome in later years?" Patients who underwent a surgical procedure for the treatment of their medically refractory epilepsy at our hospital, had more than 2-years' follow-up, and were less than 18 years old at time of survey were included. From a retrospective chart review, age at onset and at surgery, duration of seizures prior to surgery, years of follow-up, type of surgery, and neurological status were obtained. From a telephone survey, seizure frequency after surgery, marital, financial and driving status, level of education, and employment status were ascertained. Sixty-four patients in our epileptic surgical series meet entry criteria. Significantly higher levels of education, employment status and independence were found in patients with a class I Engel outcome compared to other Engel outcomes.     

Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Adaptive control of harmonic drive with parameter varying friction using structurally dynamic wavelet network

In this paper, an adaptive controller with structurally dynamic wavelet network is developed for a harmonic drive subject to parameter varying friction. The control architecture integrates a proportional controller, a feedback adaptive component and sliding component to adaptively compensate for the friction to achieve accurate position tracking. Global asymptotic stability of the algorithm is proved by using Lyapunov function. In parallel to the adaptive controller, a fuzzy reconfiguration scheme is devised to change the structure of the network along with weights updating to improve the system tracking performance and robustness. Experimental tests on a harmonic drive manipulator verify the effectiveness of the proposed control method.     

On the complexity of deciding avoidability of sets of partial words

Blanchet-Sadri et al. have shown that Avoidability, or the problem of deciding the avoidability of a finite set of partial words over an alphabet of size k≥2, is NP-hard [F. Blanchet-Sadri, R. Jungers, J. Palumbo, Testing avoidability on sets of partial words is hard, Theoret. Comput. Sci. 410 (2009) 968-972]. Building on their work, we analyze in this paper the complexity of natural variations on the problem. While some of them are NP-hard, others are shown to be efficiently decidable. Using some combinatorial properties of de Bruijn graphs, we establish a correspondence between lengths of cycles in such graphs and periods of avoiding words, resulting in a tight bound for periods of avoiding words. We also prove that Avoidability can be solved in polynomial space, and reduces in polynomial time to the problem of deciding the avoidability of a finite set of partial words of equal length over the binary alphabet. We give a polynomial bound on the period of an infinite avoiding word, in the case of sets of full words, in terms of two parameters: the length and the number of words in the set. We give a polynomial space algorithm to decide if a finite set of partial words is avoided by a non-ultimately periodic infinite word. The same algorithm also decides if the number of words of length n avoiding a given finite set of partial words grows polynomially or exponentially with n.