Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

Seeking the truth about ad hoc join costs

In this paper, we re-examine the results of prior work on methods for computing ad hoc joins. We develop a detailed cost model for predicting join algorithm performance, and we use the model to develop cost formulas for the major ad hoc join methods found in the relational database literature. We show that various pieces of “common wisdom” about join algorithm performance fail to hold up when analyzed carefully, and we use our detailed cost model to derive op timal buffer allocation schemes for each of the join methods examined here. We show that optimizing their buffer allocations can lead to large performance improvements, e.g., as much as a 400% improvement in some cases. We also validate our cost model's predictions by measuring an actual implementation of each join algorithm considered. The results of this work should be directly useful to implementors of relational query optimizers and query processing systems. Edited by M. Adiba. Received May 1993 / Accepted April 1996     

A simplified method for the preparation of succinimidyl carbonate polyethylene glycol for coupling to proteins

An improved method for the activation of polyethylene glycol with commercially available succinimidyl carbonate is described. The activated polyethylene glycol was coupled to proteins in high yield.     

Molecular simulation of temperature-programmed desorption

We use accelerated molecular dynamics to probe the thermal desorption of n-alkanes from the Au(1 1 1) and C(0 0 0 1) surfaces. Studying an alkane series ranging from CH₄ to C₁₆H₃₄, we find that the desorption prefactor increases with increasing chain length for the short chains until a certain chain length is reached when it becomes essentially constant and independent of chain length. We can understand the dependence of the preexponential factor on alkane chain length in terms of conformational changes within the alkane molecules. For the shorter molecules, the desorption temperatures probed in experimental temperature-programmed desorption studies lie below those for which torsional motion is activated. Thus, the short alkanes can be treated as rigid rods, and the loss in translational and rotational entropy upon adsorption leads to a preexponential factor that increases with increasing chain length. As the alkane chain length increases, the binding energy and the experimental desorption temperatures also increase. Thus, torsional motion is activated to an extent that increases with increasing chain length. This torsional activation increases the entropy of adsorption and counteracts the entropy decrease due to a loss of translation and rotation. This leads to a virtually constant prefactor for sufficiently long chains. Our findings are consistent with experimental data for the thermal desorption of alkanes from the Au(1 1 1), Pt(1 1 1), MgO(1 0 0) and C(0 0 0 1) surfaces.     

Interplay between Humoral and CLA+ T Cell Response against Candida albicans in Psoriasis

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA⁻ cutaneous lymphocyte antigen (CLA)^+/− T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA⁺ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA⁺ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.     

Evaluation of hydrogen bonding ability of liquids and solids by C-13 NMR. Silica gel as a strong hydrogen bond donor

The chemical shift difference between signals of C() and C() of unsaturated ketones, , which we used before to measure acid strengths, has now been used to evaluate the hydrogen bond donor ability of solvents which are not acidic enough to hydronate the indicator. For such solvents there is no general correlation between H-bond donor ability and acid strength: hexa-fluoroisopropanol is a much weaker acid than acetic acid, but it is a stronger H-bond donor. The method can be applied to evaluate the H-bonding properties of solid surfaces, and it was thus found that silica gel has a much stronger H-bond donor ability than methanol or acetic acid.     

Predicting user’s preferences using neural networks and psychology models

In this paper we describe a new model suitable for optimization problems with explicitly unknown optimization functions using user’s preferences. The model addresses an ability to learn not known optimization functions thus perform also a learning of user’s preferences. The model consists of neural networks using fuzzy membership functions and interactive evolutionary algorithms in the process of learning. Fuzzy membership functions of basic human values and their priorities were prepared by utilizing Schwartz’s model of basic human values (achievement, benevolence, conformity, hedonism, power, security, self-direction, stimulation, tradition and universalism). The quality of the model was tested on “the most attractive font face problem” and it was evaluated using the following criteria: a speed of optimal parameters computation, a precision of achieved results, Wilcoxon signed rank test and a similarity of letter images. The results qualify the developed model as very usable in user’s preference modeling.     

A SAT Solver Using Reconfigurable Hardware and Virtual Logic

In this paper, we present the architecture of a new SAT solver using reconfigurable logic and a virtual logic scheme. Our main contributions include new forms of massive fine-grain parallelism, structured design techniques based on iterative logic arrays that reduce compilation times from hours to minutes, and a decomposition technique that creates independent subproblems that may be concurrently solved by unconnected FPGAs. The decomposition technique is the basis of the virtual logic scheme, since it allows solving problems that exceed the hardware capacity. Our architecture is easily scalable. Our results show several orders of magnitude speedup compared with a state-of-the-art software implementation, and also with respect to prior SAT solvers using reconfigurable hardware.     

Verifying Temporal Properties of Reactive Systems: A STeP Tutorial

We review a number of formal verification techniques supported by STeP, the Stanford Temporal Prover, describing how the tool can be used to verify properties of several versions of the Bakery Mutual exclusion algorithm for mutual exclusion. We verify the classic two-process algorithm and simple variants, as well as an atomic parameterized version. The methods used include deductive verification rules, verification diagrams, automatic invariant generation, and finite-state model checking and abstraction.