The improvement in behavior correlated with an increase in synapt

The improvement in behavior correlated with an increase in synaptophysin and glutamic acid decarboxylase (GAD) in the spinal cord at the level of injury. Addition of recombinant GDNF protein to primary spinal cord neurons in-vitro resulted in enhanced neurite growth and a marked increase in protein levels of GAD65 and GAD67, synapsin I and synaptophysin.

GDNF-mediated increases in GAD and the synaptic markers were blocked by the MEK inhibitor UO126, but not by the phosphoinositide 3-kinase inhibitor LY294002. These results suggest that GDNF, acting through the MEK-ERK pathway enhances axonal sprouting, synaptic connectivity, this website and GABAergic neurotransmission in the spinal cord, that result in improved behavioral outcomes after spinal cord contusion injury.”
“The zero-sum assumption is one of the ingredients of the standard neutral model of biodiversity by Hubbell. It states that the community is saturated all the time, which in this model means that the total number of individuals in the community is constant over time, and therefore introduces a coupling between species abundances. It was shown recently that a neutral model with independent species, and thus without any coupling between species abundances, has the same sampling formula (given a fixed number of individuals in the sample) as the standard model [Etienne, R.S., Alonso, D., McKane, A.J., 2007. The

zero-sum assumption in neutral biodiversity theory. J. Theor. Biol. 248, 522-536]. The equilibria of both models PCI-32765 purchase are therefore S63845 manufacturer equivalent from a practical point of view. Here we show that this equivalence can be extended to a class of neutral models with density-dependence on the community-level. This result can be interpreted as robustness of the model, i.e. insensitivity of the model to the precise interaction of the species

in a neutral community. It can also be interpreted as a lack of resolution, as different mechanisms of interactions between neutral species cannot be distinguished using only a single snapshot of species abundance data. (C) 2008 Elsevier Ltd. All rights reserved.”
“In the midst of health care reform, eligible but uninsured children remain a cause for concern. Children in the same family often have differing eligibility status for public coverage. Mixed eligibility is associated with higher uninsurance rates, even when all children in a family are eligible. Medicaid policies play an important role in creating mixed-eligibility families via age-related eligibility thresholds and limited benefits for immigrants; states running separate Children’s Health Insurance Program ( CHIP) programs have higher uninsurance rates among eligible children. Recent policies to simplify enrollment have not lowered uninsurance among these children. States may improve take-up rates by focusing on eligible children in mixed-eligibility families.

METHODS We evaluated 102 patients with stable chest pain and

\n\nMETHODS We evaluated 102 patients with stable chest pain and both 64-detector row coronary CTA and quantitative invasive coronary angiography. The diagnostic performance of remote coronary CTA interpretation was assessed using selleck chemicals a mobile handheld device and employing dedicated software. The coronary CTA studies were examined in an intent-to-diagnose manner for the presence or absence

of coronary artery stenosis >= 50% on a per-artery and per-patient level; results were compared with quantitative invasive coronary angiography. Two blinded imagers independently interpreted coronary CTA studies, with a third imager achieving consensus for discordance. Coronary CTAs were re-interpreted in random order to determine interobserver agreement. Finally, coronary CTAs were evaluated on a dedicated 3-dimensional imaging workstation; results were compared to mobile handheld device findings for intertechnology agreement.\n\nRESULTS The prevalence of significant coronary artery stenosis was 25% (26 of 102) at the per-patient level and 10% (40 of 405) at the per-artery level. Per-patient

10058-F4 mw and per-artery sensitivity, specificity, and positive and negative predictive values were: 100% (26 of 26), 78% (59 of 76), 60% (26 of 43), and 100% (59 of 59), respectively; and 95% (38 of 40), 85% (310 of 365), 41% (38 of 93), and 99% (310 of 312), respectively. At the per-artery level, interobserver, intraobserver, and intertechnology learn more agreement was 0.74, 0.89, and 0.75, respectively (p < 0.01 for all).\n\nCONCLUSIONS The interpretation of coronary CTA using a mobile handheld device with dedicated software for medical image evaluation possesses high diagnostic accuracy for detection and exclusion of significant

coronary stenosis. (J Am Coll Cardiol Img 2010; 3: 482-90) (C) 2010 by the American College of Cardiology Foundation”
“We present a quantitative physical model for glass substrate polarization and study the glass polarization by measuring the capacitance drift from microelectromechanical capacitor test structure. The model consists of mobile and immobile charge species, which are related to alkali metals and non-bridging oxygen in glass. The model explains consistently our results and the previously observed non-homogeneous charging effect in a radio-frequency switch fabricated on a glass substrate. The results indicate that the bulk properties of the glass layer itself can be a significant source of drift. The modeling allows estimation of the drift behavior of the several kinds of device structures. (C) 2012 American Institute of Physics. [hap://]“
“Obesogens are chemicals that directly or indirectly lead to increased fat accumulation and obesity. Obesogens have the potential to disrupt multiple metabolic signalling pathways in the developing organism that can result in permanent changes in adult physiology.

“We report results on a dimensionally gradient magnetoelec

“We report results on a dimensionally gradient magnetoelectric (ME) sensor that demonstrates high performance over a wide frequency LY2835219 mw range and a magnetic dc bias operating in the longitudinal-transversal mode. The design of the sensor is based on a piezoelectric bimorph structure and utilizes a laminate configuration with

Pb(Zn1/3Nb2/3)(0.2)(Zr0.5Ti0.5)(0.8)O-3 and Metglas as material layers. The wide-band behavior was characterized by a flat ME response over a wide range of magnetic dc biases corresponding to 60-215 Oe and frequencies corresponding to 7-22 kHz. By using tip mass, the wide-band frequency response was shifted to a lower frequency range of 5-14 kHz. The results show that the operating frequency range of the sensor can be easily shifted by changing the tip mass at the end of the composite.”
“A wide range of techniques have been described for ankle arthrodesis,

and although all of these have been shown to provide stability, few have been shown to achieve a solid construct in patients at risk of nonunion. In this technical guide, we describe a modified transfibular approach to ankle arthrodesis that uses a fibularonlay strut graft for use in patients at high risk for nonunion. In our experience, the technique has been effective and reliable. (C) 2010 by the American College of Foot and Ankle Surgeons. All rights reserved.”
“Brain perfusion tracers like [Tc-99m] d,l-hexamethyl-propyeneamine oxime (Tc-99m-HMPAO) and [Tc-99m] ethyl-cysteinate dimer (Tc-99m-ECD) underestimate regional cerebral blood flow (rCBF) at high flow values. To improve linearity between tracer Napabucasin mouse accumulation and rCBF, two different models have been proposed. One is Lassen’s correction algorithm for back-diffusion of tracer, and the other is based on the permeability-surface (PS) model

for correction of low first-pass extraction. Although both these models have the same goal, they have completely different forms of equation. It was demonstrated that mathematical approximation of the PS model equation leads to Lassen’s equation. Napabucasin datasheet In this process, the relationship between PS, CBF values and Lassen’s parameter was acquired, and how to correct both the back-diffusion and low first-pass extraction was also demonstrated. A computer simulation confirmed that the two models provided similar consequences when the parameter value is chosen according to the relationship found. Lassen’s equation can be used to correct not only back-diffusion but also low first-pass extraction. To perform overall correction, the parameter value we have been using for decades may be too weak. I estimated that the parameter value for overall correction of HMPAO would be around 0.5, and that of ECD would be around 0.65.”
“A sound understanding of the taxonomy of threatened species is essential for setting conservation priorities and the development of management strategies.

Human astrocytes were treated with alpha-syn at different concent

Human astrocytes were treated with alpha-syn at different concentrations and time points to determine the effective membrane permeability of the peptide. After alpha-syn treatment, selleck inhibitor we analyzed apoE and cholesterol levels in the astrocyte membrane. Lastly, we performed immunocytochemistry for CFAP in control and alpha-syn treated cells. Our results indicate membrane apoE was reduced and redistributed from a nuclear and membranous dominated expression to the cytosol. Cholesterol levels were also reduced in the astrocyte cell membrane.

GFAP expression was sharply increased in alpha-syn treated cells indicating that alpha-syn may contribute to reactive gliosis. Our results support the conclusion that: astrocytes play a role in pathological mechanisms in synucleinopathies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Systematic isolation of microbial metabolites has been performed to construct microbial metabolite libraries or fraction libraries. A novel macrolactam, verticilactam (1), was isolated from a library of Streptomyces spiroverticillatus JC-8444 The structure was determined on the basis of NMR and mass spectrometric measurements. 1 had a unique 16-membered macrolactam skeleton including a beta-keto-amide moiety”
“Purpose. We report a case of focal myelinated nerve fiber (MNF) loss caused by anterior ischemic optic neuropathy.\n\nCase

Report. A 62-year-old woman with segmental MNF presented with anterior ischemic optic neuropathy. One year later, MNF lost superiorly, with preservation of inferior segment MNF. Spectral-domain optical FG-4592 price coherence tomography of the optic nerve head and posterior pole retinal thickness showed localized thinning of superior nerve fibers (axons) and retinal thickness.\n\nConclusions. This case highlights the focal nature of anterior

ischemic optic neuropathy and may be the first patient in whom sectoral loss of myelinated nerve fiber has been photographically documented. (Optom Vis Sci 2013; 90: e138-e141)”
“Objective. To investigate the clinical features of paranasal sinus osteomas and to estimate the growth rate of these tumors in a large series of patients.\n\nDesign. Case series with chart review.\n\nSetting. University hospital, tertiary referral center.\n\nSubjects and Methods. The authors BEZ235 clinical trial retrospectively reviewed the paranasal sinus tomography scans that were taken between January 1997 and April 2008 to find patients with paranasal sinus osteomas. A questionnaire was performed to evaluate the possible clinical symptoms associated with sinus osteomas, and control paranasal sinus computed tomography was taken for patients in whom paranasal computed tomography examination had been done at least 1 year ago.\n\nResults. A total of 17,154 paranasal sinus computed tomographies of 14,137 patients were reviewed, and 243 cases of paranasal sinus osteomas were found.

Methods: Five children (aged 1-9 months) harboring interhemispher

Methods: Five children (aged 1-9 months) harboring interhemispheric arachnoid cysts underwent the procedure. The neuroendoscopic technique included cystoventriculostomy and cystocisternostomy. Imaging exams were compared before and after surgery, and the differences in cyst diameters were calculated. Head circumference and neurological development were also evaluated. Results: The cystoventriculostomy was performed through the lateral ventricle in 4 cases and through the third ventricle in 4 cases. An added cystocisternostomy was performed in 1 case. Cyst diameters were reduced in the anterior-posterior, lateral-medial

and superior-inferior planes in 22, 31 and 31% of the cases, respectively. Autophagy Compound Library research buy The rate of increasing head circumference slowed; however, all the children continued

to show slight macrocrania. There were complications in 2 cases: cerebrospinal fluid fistula was managed by lumbar puncture in 1 case and subdural collection was treated with a shunt in another single case. Conclusion: The neuroendoscopic approach to interhemispheric arachnoid cysts was effective with few complications. Copyright (C) 2013 S. Karger AG, Basel”
“Several decades of research on human cytomegalovirus Ganetespib cost (HCMV) and the principal mammalian cytomegaloviruses which to varying degrees act as models of HCMV infection, particularly murine, guinea pig and rhesus CMV, have led to the recognition of the CMVs as interesting models of persistent infection with a large and complex DNA virus, which have been highly informative of the immunology and molecular pathogenesis of the virus-host relationship in the normal host. However, it is appropriate to ask how this relative wealth of knowledge has influenced the understanding and management of clinical disease due to HCMV. This article considers the immunology of cytomegalovirus in the normal human host, and the interrelated issue of the sites of HCMV latency MGCD0103 in vitro and mechanisms of reactivation in the myeloid cell lineage, and in related in vitro model systems. The way in which this site of latency conditions the immune response, and emerging information on the special features of the adaptive immune response to HCMV during latency are also considered.

Examples of HCMV disease associated with acquired immunosuppression, principally in the context of transplantation, but also as a consequence of HIV/AIDS and immune reconstitution inflammatory syndrome, are then discussed, with a particular emphasis on how understanding the immunology of persistent infection may contribute to managing CMV disease now and in future.”
“Platinum silicide Schottky diodes formed on films of polycrystalline Si doped by phosphorus are demonstrated to be efficient and manufacturable CMOS-compatible temperature sensors for microbolometer detectors of radiation. Thin-film platinum silicide/poly-Si diodes have been produced by a CMOS-compatible process on artificial Si3N4/SiO2/Si(001) substrates simulating the bolometer cells.

Results: Both nebulizers were able to successfully aerosolise

\n\nResults: Both nebulizers were able to successfully aerosolise 1.5 mL of liposome suspension in a short period of time. The diameter and zeta-potential of the liposomes was preserved upon nebulization, and the calcein retention was above 70% in all cases.\n\nConclusions: It can, hence, be concluded that both systems, the Aeroneb Pro and the AeroProbe, are

well suited for the pulmonary delivery of liposomal formulations, with the AeroProbe having the additional advantage of allowing targeted delivery into the select regions of the lungs with a high degree of efficiency Quizartinib order and control.”
“Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between

mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates find more among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed

variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.”
“Cells of the inner ear face constant metabolic and structural stress. Exposure to intense sound or certain drugs destroys cochlea hair cells, which in mammals do not regenerate. Thus, an endogenous stress response system may exist within the cochlea to protect it from everyday stressors.

Results: the risk of an injurious fall that required hospitalisat

Results: the risk of an injurious fall that required hospitalisation doubled (risk ratio: 2.14, 95% confidence interval: 1.82 to 2.51) between first- and second-eye cataract surgery compared with the 2 years before first-eye surgery. There was a 34% increase in the number of injurious falls that required hospitalisation in the

2 years after second-eye cataract surgery compared with the 2 years before first-eye surgery (risk ratio: 1.34, 95% confidence interval: 1.16-1.55). Conclusions: there was an increased risk of injurious falls after first- and second-eye cataract surgery which has implications for the timely provision of second-eye surgery as well as appropriate refractive management between surgeries.”
“Phosphorus KPT-8602 in the +5 oxidation state (i.e., phosphate) is the most abundant form of phosphorus in the global ocean. An enigmatic pool of dissolved

phosphonate molecules, with phosphorus in the FK228 solubility dmso +3 oxidation state, is also ubiquitous; however, cycling of phosphorus between oxidation states has remained poorly constrained. Using simple incubation and chromatography approaches, we measured the rate of the chemical reduction of phosphate to P(III) compounds in the western tropical North Atlantic Ocean. Colonial

nitrogen-fixing cyanobacteria in surface waters played a critical role in phosphate reduction, but other classes of plankton, including potentially deep-water archaea, were also involved. These data are consistent with marine geochemical evidence and microbial genomic information, which together suggest the existence of a vast oceanic phosphorus redox cycle.”
“Free triterpenic acids (TTPs) present in plants are bioactive compounds exhibiting multiple nutriceutical activities. The underlying molecular mechanisms check details have only been examined in part and mainly focused on anti-inflammatory properties, cancer and cardiovascular diseases, in all of which TTPs frequently affect membrane-related proteins. Based on the structural characteristics of TTPs, we assume that their effect on biophysical properties of cell membranes could play a role for their biological activity. In this context, our study is focused on the compounds, oleanolic (3 beta-hydroxy-12-oleanen-28-oic acid, OLA), maslinic (2 alpha,3 beta-dihydroxy-12-oleanen-28-oic acid, MSL) and ursolic ((3 beta)-3-hydroxyurs-12-en-28-oic acid, URL) as the most important TTPs present in orujo olive oil.

Genes predicted to encode the siderophore (hydroxamate) biosynthe

Genes predicted to encode the siderophore (hydroxamate) biosynthesis system (SO3030 to SO3032), the Fe(III)-hydroxamate receptor (SO3033), and the Fe(III)hydroxamate reductase (SO3034) were identified in the S. oneidensis genome, and corresponding in-frame gene deletion mutants were constructed. Delta SO3031 was unable to synthesize siderophores or produce soluble

organic Fe(III) during aerobic respiration yet retained the ability to solubilize and respire Fe(III) at wild-type rates during anaerobic Fe(III) oxide respiration. Delta SO3034 retained the ability to synthesize siderophores during aerobic respiration and to solubilize and respire Fe(III) at wild-type rates during anaerobic Fe(III) oxide respiration. These findings indicate that the Fe(III)-solubilizing

organic ligands produced by S. oneidensis during anaerobic Fe(III) oxide respiration are selleck chemical not synthesized via the hydroxamate biosynthesis system and that the Fe(III)-hydroxamate reductase is not essential for respiration of Fe(III)-citrate or Fe(III)-nitrilotriacetic selleck chemicals llc acid (NTA) as an anaerobic electron acceptor.”
“The epsins are a family of adaptors involved in recruiting other endocytic proteins, binding of ubiquitylated cargo and induction of membrane curvature. These molecules bear a characteristic epsin N-terminal homology (ENTH) domain and multiple peptide motifs that mediate protein-protein interactions. We have previously demonstrated that the ENTH domain of epsin is involved in Cdc42 signaling regulation. Here, we present evidence that yeast epsin 2 (Ent2) plays a signaling role during cell division. We observed that overexpression of the ENTH domain of Ent2 (ENTH2), but not Ent1, promoted the formation of chains of cells and aberrant septa. This dominant-negative effect resulted from ENTH2-mediated interference with septin assembly pathways. We mapped the ENTH2 determinants responsible for induction of the phenotype and found them to be important for efficient binding to the septin regulatory

protein, Bem3. Supporting a physiological role for epsin 2 in cell division, the protein localized to sites of polarized growth and cytokinesis and rescued a defect in cell division induced Selleck Entinostat by Bem3 misregulation. Collectively, our findings provide a potential molecular mechanism linking endocytosis (via epsin 2) with signaling pathways regulating cell division.”
“Aim: The ability of enzymatically synthesized lauroyl glucose to disrupt fungal (Candida albicans, Candida lipolytica) and bacterial (Pseudomonas aeruginosa PAO1, Pseudomonas aureofaciens) biofilms was investigated. Methods and Results: Preformed biofilms of C. albicans and C. lipolytica in polystyrene microtitre plates were disrupted upto 45% and 65%, respectively, while P. aeruginosa and P. aureofaciens biofilms were disrupted by 51% and 57%.

Since the problem of finding double-win optimal solution is NP-co

Since the problem of finding double-win optimal solution is NP-complete,

we propose two new hybrid protection algorithms, Intra-domain Sub-path Protection (ISP) algorithm and Inter-domain End-to-end Protection (IEP) algorithm. In ISP and IEP, the hybrid protection means that the intelligent algorithm find more based on Bacterial Colony Optimization (BCO) and the heuristic algorithm are used to solve the survivability in intra-domain routing and inter-domain routing, respectively. Simulation results show that ISP and IEP have the similar comprehensive utility. In addition, ISP has better resource utilization efficiency, lower blocking probability, and higher network operator’s utility, while IEP has better user’s utility. (C) 2011 Elsevier Inc. All rights reserved.”
“On the basis of our previous identification of aberrant phosphatidylinositol-3-kinase (PI3K)/Akt signaling as a novel poor prognostic factor in neuroblastoma, we evaluated the dual PI3K/mTOR inhibitor BEZ235 Stem Cell Compound Library cost in the present study. Here, BEZ235 acts in concert with the lysosomotropic agent chloroquine (CQ) to trigger apoptosis in neuroblastoma cells in a synergistic manner, as calculated by combination index (CI < 0.5). Surprisingly, inhibition of BEZ235-induced autophagy is unlikely the primary mechanism of this synergism as reported in other cancers, since neither inhibition

of autophagosome formation by knockdown of Atg7 or Atg5 nor disruption of the autophagic flux by Bafilomycin A1 (BafA1) enhance BEZ235-induced apoptosis. BEZ235 stimulates enlargement of the lysosomal compartment and generation of reactive oxygen species (ROS), while CQ promotes lysosomal membrane permeabilization (LMP). In combination, BEZ235 and CQ cooperate to trigger LMP, Bax activation, loss of mitochondrial membrane potential (MMP) and caspase-dependent apoptosis. Lysosome-mediated apoptosis occurs in a ROS-dependent manner, as ROS scavengers significantly reduce BEZ235/CQ-induced

loss of MMP, LMP and apoptosis. There is a mitochondrial-lysosomal cross-talk, since lysosomal enzyme inhibitors significantly decrease BEZ235- and CQ-induced drop of MMP and apoptosis. In conclusion, BEZ235 and CQ act in concert to trigger LMP and lysosome-mediated HSP990 apoptosis via a mitochondrial-lysosomal cross-talk. These findings have important implications for the rational development of PI3K/mTOR inhibitor-based combination therapies.”
“Techniques that are largely used for protein interaction studies and the discovery of intracellular receptors, such as affinity-capture complex purification and the yeast two-hybrid system, may produce inaccurate data sets owing to protein insolubility, transient or weak protein interactions or irrelevant intracellular context. A versatile tool for overcoming these limitations, as well as for potentially creating vaccines and engineering peptides and antibodies as targeted diagnostic and therapeutic agents, is the phagedisplay technique.

Consequently the limits and

Consequently the limits and CUDC-907 higher level placement of the Gloeophyllales are obscure. We obtained sequence data for three protein-coding genes (rpb2, WO; tell) and three

rRNA regions (nuc-ssu, nuc-lsu, 5.8S) in 19 species of Gloeophyllales representing seven genera and analyzed them together with a diverse set of Agaricomycotina, emphasizing Polyporales. Boreostereum, which is suspected to produce a white rot, is the sister group of the rest of the Gloeophyllales, all of which produce a brown rot. Gloeophyllum contains at least two independent clades, one of which might correspond to the genus Osmoporus. White rot and resupinate fruiting bodies appear to be plesiomorphic in Gloeophyllales. Relaxed molecular clock analyses suggest that the Gloeophyllales arose in the Cretaceous, after the origin of Pinaceae.”
“The operation of a high-power nonrelativistic strapped ultra-high-frequency (UHF) multicavity magnetron with transparent cathode is simulated using the Improved Concurrent Electromagnetic Particle-in-Cell (ICEPIC) code. Results of the simulations are compared

with simulations of the same magnetron with Savolitinib chemical structure a solid cylindrical cathode. Both cathodes are explosive-emission electron sources that operate in the space-charge-limited mode of the electron extraction from the cathode. Simulations are part of an effort searching for methods and technologies that enable an increase of output microwave power of strapped nonrelativistic high-power UHF magnetrons by replacing thermionic direct-heated cathodes with a non-thermionic-emission cathode. Results of the simulations show that the anode current I-a and the output power P-out of the magnetron

with the transparent cathode are higher than I-a and P-out of the same magnetron with a solid cathode. At the same time, the electronic efficiency eta(e) of the magnetron with the transparent cathode is less, and the startup time t(s) is shorter than eta(e) and t(s) of the magnetron BKM120 supplier with the solid cathode.”
“Rate (k) and equilibrium (K) constants for the reaction of tetrahydrofuranol with a series of Mg2+ complexes of methyl triphosphate analogues, CH3O-P(O-2)-O-P(O-2)-X-PO34-, X = O, CH2, CHCH3, C(CH3)(2), CFCH3, CHF, CHCl, CHBr, CFCl, CF2, CCl2, and CBr2, forming phosphate diester and pyrophosphate or bisphosphonate in aqueous solution were evaluated by B3LYP/TZVP//HF/6-31G* quantum chemical calculations and Langevin dipoles and polarized continuum solvation models. The calculated log k and log K values were found to depend linearly on the experimental pK(a4) of the conjugate acid of the corresponding pyrophosphate or bisphosphonate leaving group. The calculated slopes of these Bronsted linear free energy relationships were beta(lg) = -0.89 and beta(eq) = -0.93, respectively. The studied compounds also followed the linear relationship Delta log k = 0.