A near-infrared fluorescent probe based on a FRET rhodamine donor linked to a cyanine acceptor for sensitive detection of intracellular pH alternations

A fluorescence resonance energy transfer (FRET)-based near-infrared fluorescent probe (B+) for double-checked sensitive detection of intracellular pH changes has been synthesized by binding a near-infrared rhodamine donor to a near-infrared cyanine acceptor through robust C-N bonds via a nucleophilic substitution reaction. To demonstrate the double-checked advantages of probe B+, a near-infrared probe (A) was also prepared by modification of a near-infrared rhodamine dye with ethylenediamine to produce a closed spirolactam residue. Under basic conditions, probe B+ shows only weak fluorescence from the cyanine acceptor while probe A displays nonfluorescence due to retention of the closed spirolactam form of the rhodamine moiety. Upon decrease in solution pH level, probe B+ exhibits a gradual fluorescence increase from rhodamine and cyanine constituents at 623 nm and 743 nm respectively, whereas probe A displays fluorescence increase at 623 nm on the rhodamine moiety as acidic conditions leads to the rupture of the probe spirolactam rings. Probes A and B+ have successfully been used to monitor intracellular pH alternations and possess pKa values of 5.15 and 7.80, respectively

Clinical Study Influence of Fever and Hospital-Acquired Infection on the Incidence of Delayed Neurological Deficit and Poor Outcome after Aneurysmal Subarachnoid Hemorrhage

Although fever and infection have been implicated in the causation of delayed neurological deficits (DND) and poor outcome after aneurysmal subarachnoid hemorrhage (SAH), the relationship between these two often related events has not been extensively studied. We reviewed these events through of our retrospective database of patients with SAH. Multivariate logistic regression was used to determine independent predictors of DND and poor outcome. A total of 186 patients were analyzed. DND was noted in 76 patients (45%). Fever was recorded in 102 patients (55%); infection was noted in 87 patients (47%). A patient with one infection was more likely to experience DND compared to a patient with no infections (adjusted OR 3.73, 95% CI 1.62, 8.59). For those with more than two infections the likelihood of DND was even greater (adjusted OR 4.24, 95% CI 1.55, 11.56). Patients with 1-2 days of fever were less likely to have a favorable outcome when compared to their counterparts with no fever (adjusted OR 0.19, 95% CI 0.06, 0.62). This trend worsened as the number of days febrile increased. These data suggest that the presence of infection is associated with DND, but that fever may have a stronger independent association with overall outcome

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Electronic communication of cells with a surface mediated by boronic acid saccharide interactions

The fabrication of a molecularly tailored surface functionalised with a saccharide binding motif, a phenyl boronic acid derivative is reported.The functionalised surface facilitated the transfer of electrons, via unique electronic interactions mediated by the presence of the boronic acid, from a macrophage cell line. This is the first example of eukaryotic cellular-electrical communication mediated by the binding of cells via their cell–surface saccharide units

Higgs Boson Theory and Phenomenology

Precision electroweak data presently favors a weakly-coupled Higgs sector as the mechanism responsible for electroweak symmetry breaking. Low-energy supersymmetry provides a natural framework for weakly-coupled elementary scalars. In this review, we summarize the theoretical properties of the Standard Model (SM) Higgs boson and the Higgs sector of the minimal supersymmetric extension of the Standard Model (MSSM). We then survey the phenomenology of the SM and MSSM Higgs bosons at the Tevatron, LHC and a future e+e- linear collider. We focus on the Higgs discovery potential of present and future colliders and stress the importance of precision measurements of Higgs boson properties.Comment: 90 pages, 31 figures. Revised version. To be published in Progress in Particle and Nuclear Physics. This paper with higher resolution figures can be found at http://scipp.ucsc.edu/~haber/higgsreview/higgsrev.p

Sequential and Coordinated Actions of c-Myc and N-Myc Control Appendicular Skeletal Development

BACKGROUND: During limb development, chondrocytes and osteoblasts emerge from condensations of limb bud mesenchyme. These cells then proliferate and differentiate in separate but adjacent compartments and function cooperatively to promote bone growth through the process of endochondral ossification. While many aspects of limb skeletal formation are understood, little is known about the mechanisms that link the development of undifferentiated limb bud mesenchyme with formation of the precartilaginous condensation and subsequent proliferative expansion of chondrocyte and osteoblast lineages. The aim of this study was to gain insight into these processes by examining the roles of c-Myc and N-Myc in morphogenesis of the limb skeleton. METHODOLOGY/PRINCIPAL FINDINGS: To investigate c-Myc function in skeletal development, we characterized mice in which floxed c-Myc alleles were deleted in undifferentiated limb bud mesenchyme with Prx1-Cre, in chondro-osteoprogenitors with Sox9-Cre and in osteoblasts with Osx1-Cre. We show that c-Myc promotes the proliferative expansion of both chondrocytes and osteoblasts and as a consequence controls the process of endochondral growth and ossification and determines bone size. The control of proliferation by c-Myc was related to its effects on global gene transcription, as phosphorylation of the C-Terminal Domain (pCTD) of RNA Polymerase II, a marker of general transcription initiation, was tightly coupled to cell proliferation of growth plate chondrocytes where c-Myc is expressed and severely downregulated in the absence of c-Myc. Finally, we show that combined deletion of N-Myc and c-Myc in early limb bud mesenchyme gives rise to a severely hypoplastic limb skeleton that exhibits features characteristic of individual c-Myc and N-Myc mutants. CONCLUSIONS/SIGNIFICANCE: Our results show that N-Myc and c-Myc act sequentially during limb development to coordinate the expansion of key progenitor populations responsible for forming the limb skeleton

Finding minimal action sequences with a simple evaluation of actions

Animals are able to discover the minimal number of actions that achieves an outcome (the minimal action sequence). In most accounts of this, actions are associated with a measure of behavior that is higher for actions that lead to the outcome with a shorter action sequence, and learning mechanisms find the actions associated with the highest measure. In this sense, previous accounts focus on more than the simple binary signal of “was the outcome achieved?”; they focus on “how well was the outcome achieved?” However, such mechanisms may not govern all types of behavioral development. In particular, in the process of action discovery (Redgrave and Gurney, 2006), actions are reinforced if they simply lead to a salient outcome because biological reinforcement signals occur too quickly to evaluate the consequences of an action beyond an indication of the outcome’s occurrence. Thus, action discovery mechanisms focus on the simple evaluation of “was the outcome achieved?” and not “how well was the outcome achieved?” Notwithstanding this impoverishment of information, can the process of action discovery find the minimal action sequence? We address this question by implementing computational mechanisms, referred to in this paper as no-cost learning rules, in which each action that leads to the outcome is associated with the same measure of behavior. No-cost rules focus on “was the outcome achieved?” and are consistent with action discovery. No-cost rules discover the minimal action sequence in simulated tasks and execute it for a substantial amount of time. Extensive training, however, results in extraneous actions, suggesting that a separate process (which has been proposed in action discovery) must attenuate learning if no-cost rules participate in behavioral development. We describe how no-cost rules develop behavior, what happens when attenuation is disrupted, and relate the new mechanisms to wider computational and biological context