Characterization of the mitochondrial active-site serine protein LACTB: filaments in the mitochondrial intermembrane space

Mitochondria have evolved from endosymbiotic alpha-proteobacteria. During the endosymbiotic process early eukaryotes dumped the major component of the bacterial cell wall, the peptidoglycan layer. Peptidoglycan is synthesized and maintained by active-site serine enzymes belonging to the penicillin-binding protein and the β-lactamase superfamily. Mammals harbor a protein named LACTB that shares sequence similarity with bacterial penicillin-binding proteins and β-lactamases. Since eukaryotes lack the synthesis machinery for peptidoglycan, the physiological role of LACTB is intriguing. Recently, LACTB has been validated in vivo to be causative for obesity, suggesting that LACTB is implicated in metabolic processes. The aim of this study was to investigate the phylogeny, structure, biochemistry and cell biology of LACTB in order to elucidate its physiological function. Phylogenetic analysis revealed that LACTB has evolved from penicillin binding-proteins present in the bacterial periplasmic space. A structural model of LACTB indicates that LACTB shares characteristic features common to all penicillin-binding proteins and β-lactamases. Recombinat LACTB protein expressed in E. coli was recovered in significant quantities. Biochemical and cell biology studies showed that LACTB is a soluble protein localized in the mitochondrial intermembrane space. Further analysis showed that LACTB preprotein underwent proteolytic processing disclosing an N-terminal tetrapeptide motif also found in a set of cell death-inducing proteins. Electron microscopy structural studies revealed that LACTB can polymerize to form stable filaments with lengths ranging from twenty to several hundred nanometers. These data suggest that LACTB filaments define a distinct microdomain in the intermembrane space. A possible role of LACTB filaments is proposed in the intramitochondrial membrane organization and microcompartmentation. The implications of these findings offer novel insight into the evolution of mitochondria. Further studies of the LACTB function might provide a tool to treat mitochondria-related metabolic diseases.

Estimation Of Properties Of Rare-Gas Solids From Compression Characteristics Of Closed-Shell Ions

We present a unified approach to repulsion in ionic and van der Waals solids based on a compressible-ion/atom model. Earlier studies have shown that repulsion in ionic crystals can be viewed as arising from the compression energy of ions, described by two parameters per ion. Here we obtain the compression parameters of the rare-gas atoms Ne. Ar. Kr and Xe by interpolation using the known parameters of related equi-electronic ions (e.g. Ar from S2-. Cl-, K- and Ca2-). These parameters fit the experimental zero-temperature interatomic distances and compressibilities of the rare-gas crystals satisfactorily. A hightemperature equation of state based on an Einstein model of thermal motions is used to calculate the thermal expansivities, compressibilities and their temperature derivatives for Ar. Kr and Xe. It is argued that an instability at higher temperatures represents the limit to which the solid can be superheated. beyond which sublimation must occur.

Searching for common threads in threadfins: phylogeography of Australian polynemids in space and time

Proper management of marine fisheries requires an understanding of the spatial and temporal dynamics of marine populations, which can be obtained from genetic data. While numerous fisheries species have been surveyed for spatial genetic patterns, temporally sampled genetic data is not available for many species. We present a phylogeographic survey of the king threadfin Polydactylus macrochir across its species range in northern Australia and at a temporal scale of 1 and 10 yr. Spatially, the overall AMOVA fixation index was Omega(st) = 0.306 (F-st' = 0.838), p < 0.0001 and isolation by distance was strong and significant (r(2) = 0.45, p < 0.001). Temporally, genetic patterns were stable at a time scale of 10 yr. However, this did not hold true for samples from the eastern Gulf of Carpentaria, where populations showed a greater degree of temporal instability and lacked spatial genetic structure. Temporal but not spatial genetic structure in the Gulf indicates demographic interdependence but also indicates that fishing pressure may be high in this area. Generally, genetic patterns were similar to another co-distributed threadfin species Eleutheronema tetradactylum, which is ecologically similar. However, the historical demography of both species, evaluated herein, differed, with populations of P. macrochir being much younger. The data are consistent with an acute population bottleneck at the last glacio-eustatic low in sea level and indicate that the king threadfin may be sensitive to habitat disturbances.

Continuously equivalent networks in state space

Schoeffler has derived continuously equivalent networks in the nodal-admittance domain. The letter derives a corresponding result in state space that combines the usefulness of Schoeffler's result and the power of the state-variable approach.

The Miocene of Western Asia; Fossil mammals at the crossroads of faunal provinces and climate regimes

Being at the crossroads of the Old World continents, Western Asia has a unique position through which the dispersal and migration of mammals and the interaction of faunal bioprovinces occurred. Despite its critical position, the record of Miocene mammals in Western Asia is sporadic and there are large spatial and temporal gaps between the known fossil localities. Although the development of the mammalian faunas in the Miocene of the Old World is well known and there is ample evidence for environmental shifts in this epoch, efforts toward quantification of habitat changes and development of chronofaunas based on faunal compositions were mostly neglected. Advancement of chronological, paleoclimatological, and paleogeographical reconstruction tools and techniques and increased numbers of new discoveries in recent decades have brought the need for updating and modification of our level of understanding. We under took fieldwork and systematic study of mammalian trace and body fossils from the northwestern parts of Iran along with analysis of large mammal data from the NOW database. The data analysis was used to study the provinciality, relative abundance, and distribution history of the closed- and open-adapted taxa and chronofaunas in the Miocene of the Old World and Western Asia. The provinciality analysis was carried out, using locality clustering, and the relative abundance of the closed- and open-adapted taxa was surveyed at the family level. The distribution history of the chronofaunas was studied, using faunal resemblance indices and new mapping techniques, together with humidity analysis based on mean ordinated hypsodonty. Paleoichnological studies revealed the abundance of mammalian footprints in several parts of the basins studied, which are normally not fossiliferous in terms of body fossils. The systematic study and biochronology of the newly discovered mammalian fossils in northwestern Iran indicates their close affinities with middle Turolian faunas. Large cranial remains of hipparionine horses, previously unknown in Iran and Western Asia, are among the material studied. The initiation of a new field project in the famous Maragheh locality also brings new opportunities to address questions regarding the chronology and paleoenvironment of this classical site. Provinciality analysis modified our previous level of understandings, indicating the interaction of four provinces in Western Asia. The development of these provinces was apparently due to the presence of high mountain ranges in the area, which affected the dispersal of mammals and also climatic patterns. Higher temperatures and possibly higher co2 levels in the Middle Miocene Climatic Optimum apparently favored the development of the closed forested environments that supported the dominance of the closed-adapted taxa. The increased seasonality and the progressive cooling and drying of the midlatitudes toward the Late Miocene maintained the dominance of open-adapted faunas. It appears that the late Middle Miocene was the time of transition from a more forested to a less forested world. The distribution history of the closed- and open-adapted chronofaunas shows the presence of cosmopolitan and endemic faunas in Western Asia. The closed-adapted faunas, such as the Arabian chronofauna of the late Early‒early Middle Miocene, demonstrated a rapid buildup and gradual decline. The open-adapted chronofaunas, such as the Late Miocene Maraghean fauna, climaxed gradually by filling the opening environments and moving in response to changes in humidity patterns. They abruptly declined due to demise of their favored environments. The Siwalikan chronofauna of the early Late Miocene remained endemic and restricted through all its history. This study highlights the importance of field investigations and indicates that new surveys in the vast areas of Western Asia, which are poorly sampled in terms of fossil mammal localities, can still be promising. Clustering of the localities supports the consistency of formerly known patterns and augments them. Although the quantitative approach to relative abundance history of the closed- and open-adapted mammals harks back to more than half a century ago, it is a novel technique providing robust results. Tracking the history of the chronofaunas in space and time by means of new computational and illustration methods is also a new practice that can be expanded to new areas and time spans.

Convex-transitive Banach spaces and their hyperplanes

The topic of this dissertation is the geometric and isometric theory of Banach spaces. This work is motivated by the known Banach-Mazur rotation problem, which asks whether each transitive separable Banach space is isometrically a Hilbert space. A Banach space X is said to be transitive if the isometry group of X acts transitively on the unit sphere of X. In fact, some weaker symmetry conditions than transitivity are studied in the dissertation. One such condition is an almost isometric version of transitivity. Another investigated condition is convex-transitivity, which requires that the closed convex hull of the orbit of any point of the unit sphere under the rotation group is the whole unit ball. Following the tradition developed around the rotation problem, some contemporary problems are studied. Namely, we attempt to characterize Hilbert spaces by using convex-transitivity together with the existence of a 1-dimensional bicontractive projection on the space, and some mild geometric assumptions. The convex-transitivity of some vector-valued function spaces is studied as well. The thesis also touches convex-transitivity of Banach lattices and resembling geometric cases.

Aspects of atomic decompositions and Bergman projections

The concept of an atomic decomposition was introduced by Coifman and Rochberg (1980) for weighted Bergman spaces on the unit disk. By the Riemann mapping theorem, functions in every simply connected domain in the complex plane have an atomic decomposition. However, a decomposition resulting from a conformal mapping of the unit disk tends to be very implicit and often lacks a clear connection to the geometry of the domain that it has been mapped into. The lattice of points, where the atoms of the decomposition are evaluated, usually follows the geometry of the original domain, but after mapping the domain into another this connection is easily lost and the layout of points becomes seemingly random. In the first article we construct an atomic decomposition directly on a weighted Bergman space on a class of regulated, simply connected domains. The construction uses the geometric properties of the regulated domain, but does not explicitly involve any conformal Riemann map from the unit disk. It is known that the Bergman projection is not bounded on the space L-infinity of bounded measurable functions. Taskinen (2004) introduced the locally convex spaces LV-infinity consisting of measurable and HV-infinity of analytic functions on the unit disk with the latter being a closed subspace of the former. They have the property that the Bergman projection is continuous from LV-infinity onto HV-infinity and, in some sense, the space HV-infinity is the smallest possible substitute to the space H-infinity of analytic functions. In the second article we extend the above result to a smoothly bounded strictly pseudoconvex domain. Here the related reproducing kernels are usually not known explicitly, and thus the proof of continuity of the Bergman projection is based on generalised Forelli-Rudin estimates instead of integral representations. The minimality of the space LV-infinity is shown by using peaking functions first constructed by Bell (1981). Taskinen (2003) showed that on the unit disk the space HV-infinity admits an atomic decomposition. This result is generalised in the third article by constructing an atomic decomposition for the space HV-infinity on a smoothly bounded strictly pseudoconvex domain. In this case every function can be presented as a linear combination of atoms such that the coefficient sequence belongs to a suitable Köthe co-echelon space.

Dynamic Instabilities in Slender Space Launch Vehicles under Propulsive Thrust and Aerodynamic Forces

A mechanics based linear analysis of the problem of dynamic instabilities in slender space launch vehicles is undertaken. The flexible body dynamics of the moving vehicle is studied in an inertial frame of reference, including velocity induced curvature effects, which have not been considered so far in the published literature. Coupling among the rigid-body modes, the longitudinal vibrational modes and the transverse vibrational modes due to asymmetric lifting-body cross-section are considered. The model also incorporates the effects of aerodynamic forces and the propulsive thrust of the vehicle. The effects of the coupling between the combustion process (mass variation, developed thrust etc.) and the variables involved in the flexible body dynamics (displacements and velocities) are clearly brought out. The model is one-dimensional, and it can be employed to idealised slender vehicles with complex shapes. Computer simulations are carried out using a standard eigenvalue problem within h-p finite element modelling framework. Stability regimes for a vehicle subjected to propulsive thrust are validated by comparing the results from published literature. Numerical simulations are carried out for a representative vehicle to determine the instability regimes with vehicle speed and propulsive thrust as the parameters. The phenomena of static instability (divergence) and dynamic instability (flutter) are observed. The results at low Mach number match closely with the results obtained from previous models published in the literature.

CFD analysis of high frequency miniature pulse tube refrigerators for space applications with thermal non-equilibrium model

High frequency, miniature, pulse tube cryocoolers are extensively used in space applications because of their simplicity. Parametric studies of inertance type pulse tube cooler are performed with different length-to-diameter ratios of the pulse tube with the help of the FLUENT (R) package. The local thermal non-equilibrium of the gas and the matrix is taken into account for the modeling of porous zones, in addition to the wall thickness of the components. Dynamic characteristics and the actual mechanism of energy transfer in pulse are examined with the help of the pulse tube wall time constant. The heat interaction between pulse tube wall and the oscillating gas, leading to surface heat pumping, is quantified. The axial heat conduction is found to reduce the performance of the pulse tube refrigerator. The thermal non-equilibrium predicts a higher cold heat exchanger temperature compared to thermal equilibrium. The pressure drop through the porous medium has a strong non-linear effect due to the dominating influence of Forchheimer term over that of the linear Darcy term at high operating frequencies. The phase angle relationships among the pressure, temperature and the mass flow rate in the porous zones are also important in determining the performance of pulse tuberefrigerator.

Geometric Representation of Graphs in Low Dimension Using Axis Parallel Boxes

An axis-parallel k-dimensional box is a Cartesian product R-1 x R-2 x...x R-k where R-i (for 1 <= i <= k) is a closed interval of the form [a(i), b(i)] on the real line. For a graph G, its boxicity box(G) is the minimum dimension k, such that G is representable as the intersection graph of (axis-parallel) boxes in k-dimensional space. The concept of boxicity finds applications in various areas such as ecology, operations research etc. A number of NP-hard problems are either polynomial time solvable or have much better approximation ratio on low boxicity graphs. For example, the max-clique problem is polynomial time solvable on bounded boxicity graphs and the maximum independent set problem for boxicity d graphs, given a box representation, has a left perpendicular1 + 1/c log n right perpendicular(d-1) approximation ratio for any constant c >= 1 when d >= 2. In most cases, the first step usually is computing a low dimensional box representation of the given graph. Deciding whether the boxicity of a graph is at most 2 itself is NP-hard. We give an efficient randomized algorithm to construct a box representation of any graph G on n vertices in left perpendicular(Delta + 2) ln nright perpendicular dimensions, where Delta is the maximum degree of G. This algorithm implies that box(G) <= left perpendicular(Delta + 2) ln nright perpendicular for any graph G. Our bound is tight up to a factor of ln n. We also show that our randomized algorithm can be derandomized to get a polynomial time deterministic algorithm. Though our general upper bound is in terms of maximum degree Delta, we show that for almost all graphs on n vertices, their boxicity is O(d(av) ln n) where d(av) is the average degree.

The effect of closed boundary conditions on a stationary dynamo

One of two boundary conditions generally assumed in solutions of the dynamo equation is related to the disappearance of the azimuthal field at the boundary. Parker (1984) points out that for the realization of this condition the field must escape freely through the surface. Escape requires that the field be detached from the gas in which it is embedded. In the case of the sun, this can be accomplished only through reconnection in the tenuous gas above the visible surface. Parker concludes that the observed magnetic activity on the solar surface permits at most three percent of the emerging flux to escape. He arrives at the conclusion that, instead of B(phi) = 0, the partial derivative of B(phi) to r is equal to zero. The present investigation is concerned with the effect of changing the boundary condition according to Parker's conclusion. Implications for the solar convection zone are discussed.

Total Hip and Knee Arthoplasty for Osteoarthritis : Factors Related to the Early Outcome of Surgery

Some perioperative clinical factors related to the primary cemented arthroplasty operation for osteoarthritis of the hip or knee joint are studied and discussed in this thesis. In a randomized, double-blind study, 39 patients were divided into two groups: one receiving tranexamic acid and the other not receiving it. Tranexamic acid was given in a dose of 10 mg/kg before the operation and twice thereafter, at 8-hour intervals. Total blood loss was smaller in the tranexamic acid group than in the control group. No thromboembolic complications were noticed. In a prospective, randomized study, 58 patients with hip arthroplasty and 39 patients with knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage. There was no difference in healing of the wounds, postoperative blood transfusions, complications or range of motion. As a result of this study, the use of drains is no longer recommended. In a randomised study the effectiveness of a femoral nerve block (25 patients) was compared with other methods of pain control (24 patients) on the first postoperative day after total knee arthroplasty. The femoral block consisted of a single injection administered at patients´ bedside during the surgeon´s hospital rounds. Femoral block patients reported less pain and required half of the amount of oxycodone. Additional femoral block or continued epidural analgesia was required more frequently by the control group patients. Pain management with femoral blocks resulted in less work for nursing staff. In a retrospective study of 422 total hip and knee arthroplasty cases the C-reactive protein levels and clinical course were examined. After hip and knee arthroplasty the maximal C-reactive protein values are seen on the second and third postoperative days, after which the level decreases rapidly. There is no difference between patients with cemented or uncemented prostheses. Major postoperative complications may cause a further increase in C-reactive protein levels at one and two weeks. In-hospital and outpatient postoperative control radiographs of 200 hip and knee arthroplasties were reviewed retrospectively. If postoperative radiographs are of good quality, there seems to be no need for early repetitive radiographs. The quality and safety of follow-up is not compromised by limiting follow-up radiographs to those with clinical indications. Exposure of the patients and the staff to radiation is reduced. Reading of the radiographs by only the treating orthopaedic surgeon is enough. These factors may seem separate from each other, but linking them together may help the treating orthopaedic surgeon to adequate patient care strategy. Notable savings can be achieved.