Intermediate Spectra Research Articles

Muscle-specific regulation of the mTOR signaling pathway in MuSK antibody seropositive (MuSK+) experimental autoimmune Myasthenia gravis (EAMG)

Myasthenia gravis (MG) patients with antibodies against muscle specific tyrosine kinase (MuSK+) typically present focal fatigue and atrophy of the facial and bulbar muscles, including the masseter muscle, whereas leg muscles often are clinically spared. This study addresses the regulation of the mTOR signaling pathway in the masseter muscle versus the leg muscle tibialis anterior (TA). We analyzed muscle morphology, protein levels of mTOR components as well as atrogenes and mitochondrial markers in these muscles of healthy control mice and mice with different clinical severity grades of MuSK+ experimental autoimmune MG (EAMG). Protein levels of mTOR components were reduced in the atrophic masseter muscle of MuSK+ EAMG mice, whereas enhanced accumulation of mTOR components was observed in the TA muscles. Two other muscles: omohyoid and soleus showed intermediate spectra. In conclusion, the anabolic mTOR signaling pathway is differentially regulated even in muscles with the same activity pattern in the same neuromuscular disease. This could in part explain the clinical phenotype in MuSK+ EAMG as well as in muscular dystrophies.

Pump power dependence in resonance femtosecond stimulated Raman spectroscopy

Femtosecond stimulated Raman spectroscopy (FSRS) has emerged as a powerful new technique that is capable of obtaining resonance Raman spectra of fluorescent species and transient photochemical intermediates. Unlike related transient infrared absorption techniques, the FSRS signal is quite sensitive to the laser power utilized in the vibrational probing event. In particular, FSRS spectra are highly sensitive to the intensity of the picosecond Raman‐pump pulse. We have measured the power dependence of the FSRS signal using pulse energies from ~10−9 to ~10−5 J and molecules with a range of molar absorptivities at the Raman‐pump wavelength of 400 nm, including β‐carotene (ε400 = 58 300 M−1 cm−1), para‐nitroaniline (17 800 M−1 cm−1), nitronaphthalene (247 M−1 cm−1) and ferrocene (57 M−1 cm−1). We show that for strongly absorbing molecular systems, such as β‐carotene and para‐nitroaniline, the ground‐state (GS) FSRS signal actually decreases with increasing pump power at pump fluences above ~10−2 J cm−2, due to depletion of the GS population. However, for weakly absorbing species like nitronaphthalene and ferrocene, the signal increases linearly with increasing pump fluence until ~0.5 J cm−2, at which point two‐photon absorption by the solute induces nonlinear absorption of the pump pulse and attenuation of the FSRS signal. The data are quantitatively simulated with a photophysical kinetic model, and the results are analyzed to provide simple guidelines for acceptable Raman‐pump powers in resonance FSRS experiments. The acceptable Raman‐pump power is proportional to the focused beam area and depends inversely on the sample's molar absorptivity. Copyright © 2013 John Wiley & Sons, Ltd.

A new technique for the determination of the initial mass function in unresolved stellar populations

We present a new technique for the determination of the low-mass slope ($\alpha_1$; $M_* < 0.5 M_{\odot}$) of the present day stellar mass function (PDMF) using the pixel space fitting of integrated light spectra. It can be used to constrain the initial mass function (IMF) of stellar systems with relaxation timescales exceeding the Hubble time and testing the IMF universality hypothesis. We provide two versions of the technique: (1) a fully unconstrained determination of the age, metallicity, and $\alpha_1$ and (2) a constrained fitting by imposing the externally determined mass-to-light ratio of the stellar population. We have tested our approach by Monte-Carlo simulations using mock spectra and conclude that: (a) age, metallicity and $\alpha_1$ can be precisely determined by applying the unconstrained version of the code to high signal-to-noise datasets (S/N=100, R=7000 yield $\Delta \alpha_1 \approx 0.1$); (b) the $M/L$ constraint significantly improves the precision and reduces the degeneracies, however its systematic errors will cause biased $\alpha_1$ estimates; (c) standard Lick indices cannot constrain the PDMF because they miss most of the mass function sensitive spectral features; (d) the $\alpha_1$ determination remains unaffected by the high-mass IMF shape ($\alpha_3$; $M_* \ge 1 M_{\odot}$) variation for stellar systems older than 8 Gyr, while the intermediate-mass IMF slope ($\alpha_2$; $0.5 \le M_* < 1 M_{\odot}$) may introduce biases into the best-fitting $\alpha_1$ values if it is different from the canonical value $\alpha_2 = 2.3$. We analysed observed intermediate resolution spectra of ultracompact dwarf galaxies with our technique and demonstrated its applicability to real data.

Increased Redox-Sensitive Green Fluorescent Protein Reduction Potential in the Endoplasmic Reticulum following Glutathione-Mediated Dimerization

As the endoplasmic reticulum (ER) is the compartment where disulfide bridges in secreted and cell surface proteins are formed, the disturbance of its redox state has profound consequences, yet regulation of ER redox potential remains poorly understood. To monitor the ER redox state in live cells, several fluorescence-based sensors have been developed. However, these sensors have yielded results that are inconsistent with each other and with earlier non-fluorescence-based studies. One particular green fluorescent protein (GFP)-based redox sensor, roGFP1-iL, could detect oxidizing changes in the ER despite having a reduction potential significantly lower than that previously reported for the ER. We have confirmed these observations and determined the mechanisms by which roGFP1-iL detects oxidizing changes. First, glutathione mediates the formation of disulfide-bonded roGFP1-iL dimers with an intermediate excitation fluorescence spectrum resembling a mixture of oxidized and reduced monomers. Second, glutathione facilitates dimerization of roGFP1-iL, which shifted the equilibrium from oxidized monomers to dimers, thereby increasing the molecule's reduction potential compared with that of a dithiol redox buffer. We conclude that the glutathione redox couple in the ER significantly increased the reduction potential of roGFP1-iL in vivo by facilitating its dimerization while preserving its ratiometric nature, which makes it suitable for monitoring oxidizing and reducing changes in the ER with a high degree of reliability in real time. The ability of roGFP1-iL to detect both oxidizing and reducing changes in ER and its dynamic response in glutathione redox buffer between approximately -190 and -130 mV in vitro suggests a range of ER redox potentials consistent with those determined by earlier approaches that did not involve fluorescent sensors.

Copper‐Catalyzed Oxidative Coupling of Carboxylic Acids with N,N‐Dialkylformamides: An Approach to the Synthesis of Amides

After consultation with the author, the Supporting Information file for the original article1 has been replaced to comply with our policy that 1H and 13C NMR spectra of all key intermediates and all final products should be included in the Supporting Information. The changes do not affect any of the conclusions of the article. The Editor

Radiolysis of sodium p-cumenesulfonate in aqueous solution

The reactions of hydrated electron eaq−, hydrogen atom (H) and CO2− (reducing species) as well as Cl2−, Br2−, N3−, OH, O−, SO4− radicals (oxidizing species) with sodium p-cumenesulfonate (SCS) in aqueous solution below minimum hydrotrope concentration have been studied by the method of steady-state and pulse radiolysis. The spectra of transient intermediates, leading to the final products, are presented. The rate constants for the reduction or oxidation reaction of the SCS are also given. The fate of the primary products of the SCS reaction produced during the pulse radiolysis under reductive or oxidative conditions is discussed.

Effect of Hofmeister cosolutes on the photocycle of photoactive yellow protein at moderately alkaline pH

The photocycle of photoactive yellow protein was studied by kinetic absorption spectroscopy from below 100ns to seconds, at moderately alkaline pH, in the presence of high concentrations of various salts. Chemometric analysis combined with multiexponential fit of the flash-induced difference spectra provided evidence for five intermediates, including a spectrally silent form before the final recovery of the parent state, but only three with significantly distinct spectra. The calculated intermediate spectra constituted the input for the following spectrotemporal model fit using a sufficiently complex photocycle scheme with reversible transitions. This yielded the rate coefficients of the molecular transitions, the final spectra and the kinetics of the intermediates. Except for the transition between the two red shifted (early) intermediates (pR1 and pR2) and the final photocycle step, all reactions appeared to be reversible. Kosmotropic and chaotropic cosolutes had a systematic effect on the molecular rate coefficients. The largest effect, associated presumably with the exposure of the hydrophobic interior of the protein, accompanies the transition between the second red-shifted and the first blue-shifted intermediate (pR2 and pB1, respectively), i.e. it coincides with the chromophore protonation. The dependence of the rate coefficients on the Hofmeister cosolutes suggests that the conformational change of photoactive yellow protein leading eventually to the most unfolded signaling state takes place in several steps, and starts already with the relaxation after the chromophore isomerization in the microsecond time domain.

Calculated and Experimental Regularities of Cloud Microstructure Formation and Evolution

Based on the model of regular condensation it was found that at low concentrations of CN (LC mode) at a height of about 10 m from the condensation level narrow spectra of cloud drop are formed. Their dispersion quickly decreases with increasing height. For high concentrations (HC mode) broad spectra are formed immediately due to the absence of separation into growing drops and CN covered with water. The process of spectra evolution is conducted at a constant height results, in all the cases, in the appearance of asymptotic spectra with a relative width rb ≥ 0.215. To approximate these calculated asymptotic spectra, the modified gamma-distribution with the fixed parameter α = 3 and a variable parameter γ are most suitable. For the intermediate spectra applicable are the simpler mirror-transformed known distributions. The comparison of the above distributions with the experimental spectra of a fog artificially formed in the Big Aerosol Chamber (BAC) of RPA “Typhoon” and the spectra of the morning fog and super cooled stratiform clouds demonstrated their good agreement. The phenomenon of multimodal spectra formation at a sharp rise of stratiform clouds with the velocity more than 0.1 - 0.3 m/s was theoretically shown and experimentally confirmed. The effect of CN high concentrations, evolution processes and sharp fluctuations of vertical velocities on the formation of cloud spectra observed in nature is discussed.

Oxidative degradation of fensulfothion by hydroxyl radical in aqueous medium

Oxidative degradation of fensulfothion, a model organophosphorus compound, has been investigated by pulse radiolysis and H2O2/UV photolysis. A nearly complete transformation of fensulfothion was observed within 4min of irradiation. Very little Total Organic Carbon (TOC) reduction was obtained at this time scale. When the product studies at this stage were conducted using LC–MS/MS analyses, nearly 20 transformation products were obtained. The entire products were identified as from the reaction of OH with fensulfothion or with some of its initially transformed products. Nearly 80% reduction in TOC was observed when photolysis was conducted using higher concentrations of H2O2 at longer time scale. A reaction rate constant (bimolecular) of 1.10×1010dm3mol−1s−1 was obtained for the reaction of OH with fensulfothion using pulse radiolysis technique. The transient absorption spectrum obtained from the reaction of OH has a maximum at 280nm and a weak, broad maximum around 500nm along with a small shoulder around 340nm. The intermediate spectrum is assigned to the radical cation of fensulfothion (3) and the hydroxyl radical adducts (1 and 2). This assignment is supported by the intermediate spectrum (λmax at 280nm) from the reaction of sulfate radical anion (SO4-) (k2=3.20×109dm3mol−1s−1) which is a one electron oxidant. It is thus demonstrated that the combination of both pulse radiolysis and the product estimation using LC–MS/MS is ideal in probing the complete mechanism which is very important in the mineralization reactions using Advanced Oxidation Processes.

Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1.1 with MCNP6

Recent releases of three major world nuclear reaction data libraries, ENDF/B-VII.1, JENDL-4.0, and JEFF-3.1.1, have been tested extensively using benchmark calculations. The calculations were performed with the latest release of the continuous energy Monte Carlo neutronics code MCNP, i.e. MCNP6. Three types of benchmarks were used, viz. criticality safety benchmarks, (fusion) shielding benchmarks, and reference systems for which the effective delayed neutron fraction is reported.For criticality safety, more than 2000 benchmarks from the International Handbook of Criticality Safety Benchmark Experiments were used. Benchmarks from all categories were used, ranging from low-enriched uranium, compound fuel, thermal spectrum ones (LEU-COMP-THERM), to mixed uranium-plutonium, metallic fuel, fast spectrum ones (MIX-MET-FAST). For fusion shielding many benchmarks were based on IAEA specifications for the Oktavian experiments (for Al, Co, Cr, Cu, LiF, Mn, Mo, Si, Ti, W, Zr), Fusion Neutronics Source in Japan (for Be, C, N, O, Fe, Pb), and Pulsed Sphere experiments at Lawrence Livermore National Laboratory (for 6Li, 7Li, Be, C, N, O, Mg, Al, Ti, Fe, Pb, D2O, H2O, concrete, polyethylene and teflon). The new functionality in MCNP6 to calculate the effective delayed neutron fraction was tested by comparison with more than thirty measurements in widely varying systems. Among these were measurements in the Tank Critical Assembly (TCA in Japan) and IPEN/MB-01 (Brazil), both with a thermal spectrum, two cores in Masurca (France) and three cores in the Fast Critical Assembly (FCA, Japan), all with fast spectra.The performance of the three libraries, in combination with MCNP6, is shown to be good. The results for the LEU-COMP-THERM category are on average very close to the benchmark value. Also for most other categories the results are satisfactory. Deviations from the benchmark values do occur in certain benchmark series, or in isolated cases within benchmark series. Such instances can often be related to nuclear data for specific non-fissile elements, such as C, Fe, or Gd. Indications are that the intermediate and mixed spectrum cases are less well described.The results for the shielding benchmarks are generally good, with very similar results for the three libraries in the majority of cases. Nevertheless there are, in certain cases, strong deviations between calculated and benchmark values, such as for Co and Mg. Also, the results show discrepancies at certain energies or angles for e.g. C, N, O, Mo, and W.The functionality of MCNP6 to calculate the effective delayed neutron fraction yields very good results for all three libraries.

Spectral Identification of Intermediates Generated during the Reaction of Dioxygen with the Wild-Type and EQ(I-286) Mutant of Rhodobacter sphaeroides Cytochrome c Oxidase

Cytochrome c oxidase from Rhodobacter sphaeroides is frequently used to model the more complex mitochondrial enzyme. The O(2) reduction in both enzymes is generally described by a unidirectional mechanism involving the sequential formation of the ferrous-oxy complex (compound A), the P(R) state, the oxyferryl F form, and the oxidized state. In this study we investigated the reaction of dioxygen with the wild-type reduced R. sphaeroides cytochrome oxidase and the EQ(I-286) mutant using the CO flow-flash technique. Singular value decomposition and multiexponential fitting of the time-resolved optical absorption difference spectra showed that three apparent lifetimes, 18 μs, 53 μs, and 1.3 ms, are sufficient to fit the kinetics of the O(2) reaction of the wild-type enzyme. A comparison of the experimental intermediate spectra with the corresponding intermediate spectra of the bovine enzyme revealed that P(R) is not present in the reaction mechanism of the wild-type R. sphaeroides aa(3). Transient absorbance changes at 440 and 610 nm support this conclusion. For the EQ(I-286) mutant, in which a key glutamic residue in the D proton pathway is replaced by glutamine, two lifetimes, 16 and 108 μs, were observed. A spectral analysis of the intermediates shows that the O(2) reaction in the EQ(I-286) mutant terminates at the P(R) state, with 70% of heme a becoming oxidized. These results indicate significant differences in the kinetics of O(2) reduction between the bovine and wild-type R. sphaeroides aa(3) oxidases, which may arise from differences in the relative rates of internal electron and proton movements in the two enzymes.

Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites

Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now prioritized for functional study.

Methionine Residue Acts as a Prooxidant in the •OH-Induced Oxidation of Enkephalins

Enkephalins are bioactive pentapeptides (Tyr-Gly-Gly-Phe-Leu (Leu-enk) and Tyr-Gly-Gly-Phe-Met (Met-enk)) produced while an organism is under mental and/or physical stress. In the course of their biological action they are exposed to reactive oxygen and nitrogen species. We have reinvestigated the reactions of (•)OH radicals toward these peptides in order to elucidate the oxidation mechanisms and the final products. Nanosecond pulse radiolysis was used to obtain the spectra of the reaction intermediates and their kinetics. Additional insight into details of the oxidation mechanism was gained by identification of main final products by means of UV-vis spectrophotometry, HPLC coupled with fluorescence spectroscopy, and mass spectrometry. The key processes are different in both peptides. In Leu-enk, the first step is an (•)OH radical addition to the aromatic rings of Tyr and Phe residues that leads to hydroxylated residues, dihydroxyphenylalanine (DOPA) from Tyr and tyrosine isomers from Phe, respectively. In Met-enk, these processes are less important, an additional target being the sulfur atom of the methionine residue. Depending on pH either an OH-adduct (hydroxysulfuranyl radical) or a sulfur radical cation undergo intramolecular electron transfer with Tyr residue resulting in a repair of Met and oxidation of Tyr to tyrosyl radicals and a final formation of dityrosine. At low pH, the OH-adducts to Tyr residue are precursors of tyrosyl radicals and dityrosine. Thus, the final products coming from oxidation of the Tyr residue depend strongly on the neighboring residues and the pH.

Structure Changes upon Deprotonation of the Proton Release Group in the Bacteriorhodopsin Photocycle

In the photocycle of bacteriorhodopsin at pH 7, a proton is ejected to the extracellular medium during the protonation of Asp-85 upon formation of the M intermediate. The group that releases the ejected proton does not become reprotonated until the prephotolysis state is restored from the N and O intermediates. In contrast, at acidic pH, this proton release group remains protonated to the end of the cycle. Time-resolved Fourier transform infrared measurements obtained at pH 5 and 7 were fitted to obtain spectra of kinetic intermediates, from which the spectra of M and N/O versus unphotolyzed state were calculated. Vibrational features that appear in both M and N/O spectra at pH 7, but not at pH 5, are attributable to deprotonation from the proton release group and resulting structural alterations. Our results agree with the earlier conclusion that this group is a protonated internal water cluster, and provide a stronger experimental basis for this assignment. A decrease in local polarity at the N-C bond of the side chain of Lys-216 resulting from deprotonation of this water cluster may be responsible for the increase in the proton affinity of Asp-85 through M and N/O, which is crucial for maintaining the directionality of proton pumping.

Pulse radiolysis study of the reactions of catechins with nitrogen dioxide

Nitrogen dioxide (•NO2), one of the oxidizing radicals formed in vivo is suspected to play a role in various pathophysiological processes. The reactions of •NO2 with dietary catechins, the group of flavonoids present in high amounts in green tea and red wine, have been investigated by pulse radiolysis method. The kinetics of the reaction of •NO2 with gallic acid have been also studied for comparison. The spectra of transient intermediates are presented. The rate constants of the reaction of •NO2 with catechin, epigallocatechin, epigallocatechin gallate and gallic acid determined by the competition method with 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulfonate) at pH 7.0 and room temperature have been found to be 0.9, 1.0, 2.3 and 0.5×108M−1s−1, respectively. The values for catechins are among the highest reported for the reactions of •NO2 with non-radical compounds.

Synthetic Reaction Mechanism of Octogen by Chemometrics and Infrared Spectroscopy

Online IR spectrum was used for monitoring the reaction process of synthesizing octogen(HMX).The concentration profiles and IR spectra of reactants,intermediates and product were determined by analyzing the spectral data using multivariate curve resolution-alternating least squares(MCR-ALS) and heuristic evolving latent projection(HELP),and the reasonable mechanism was deduced.The stable geometry of intermediates was optimized at B3LYP/6-31G* theoretical level.Its vibrational frequencies and IR spectra were obtained on the basis of vibrational analysis.The results showed that the variation of intermediates could be obtained quickly with the aid of chemometric resolution and provided significant guidance to the choice of reaction.

Aluminum abundances of multiple stellar generations in the globular cluster NGC 1851

We study the distribution of aluminum abundances among red giants in the peculiar globular cluster NGC 1851. Aluminum abundances were derived from the strong doublet Al I 8772-8773 A measured on intermediate resolution FLAMES spectra of 50 cluster stars acquired under the Gaia-ESO public survey. We coupled these abundances with previously derived abundance of O, Na, Mg to fully characterize the interplay of the NeNa and MgAl cycles of H-burning at high temperature in the early stellar generation in NGC 1851. The stars in our sample show well defined correlations between Al,Na and Si; Al is anticorrelated with O and Mg. The average value of the [Al/Fe] ratio steadily increases going from the first generation stars to the second generation populations with intermediate and extremely modified composition. We confirm on a larger database the results recently obtained by us (Carretta et al. 2011a): the pattern of abundances of proton-capture elements implies a moderate production of Al in NGC 1851. We find evidence of a statistically significant positive correlation between Al and Ba abundances in the more metal-rich component of red giants in NGC 1851.

The first detailed experimental investigation of the KMM + KMN Auger electron spectrum of Cu emitted in the EC decay of radioactive 65Zn in a solid state matrix

The KMM + KMN Auger spectrum of Cu emitted in the electron capture decay of radioactive 65Zn in a solid state matrix was investigated for the first time at the instrumental energy resolution of 14 eV. Energies and relative intensities of twelve resolved spectrum components were determined and compared with theoretical predictions. A reasonable agreement of the semi-empirical calculations of transition energies by Larkins with experiment was observed. A comparison of theoretical and the measured transition rates indicates the important role of a coupling scheme applied. A more detailed analysis was hampered by absence of theoretical intensities for the individual intermediate coupling spectrum components. A slight indication of the influence of the source backing material on the absolute energies was found for the L3M4, 5M4, 5 and L2M4, 5M4, 5 Auger lines.

Automatic Baseline Subtraction of Vibrational Spectra Using Minima Identification and Discrimination via Adaptive, Least-Squares Thresholding

A method of automated baseline correction has been developed and applied to Raman spectra with a low signal-to-noise ratio and surface-enhanced infrared absorption (SEIRA) spectra with bipolar bands. Baseline correction is initiated by dividing the raw spectrum into equally spaced segments in which regional minima are located. Following identification, the minima are used to generate an intermediate second-derivative spectrum where points are assigned as baseline if they reside within a locally defined threshold region. The threshold region is similar to a confidence interval encountered in statistics. To restrain baseline and band point discrimination to the local level, the calculation of the confidence region employs only a predefined number of already-accepted baseline minima as part of the sample set. Statistically based threshold criteria allow the procedure to make an unbiased assessment of baseline points regardless of the behavior of vibrational bands. Furthermore, the threshold region is adaptive in that it is further modified to consider abrupt changes in baseline. The present procedure is model-free insofar as it makes no assumption about the precise nature of the perturbing baseline nor requires treatment of spectra prior to execution.

A Performance based Routing Classification in Cognitive Radio Networks

Cognitive Radio Networks (CRN) is offering tremendous performance and operational benefit by providing high bandwidth to mobile users via dynamic spectrum access techniques. In this paper, we address the problem of routing in CRN which concerns about identification and maintenance of the optimal path from source to destination through intermediate relay nodes and spectrum on each link using available common channels. In this survey, the characteristics features and limiting factors of existing routing protocols are thoroughly investigated with its performance evaluation criteria's. First, the overview of the routing with its unique challenges is given under the restriction of interference and fairness to increase overall network throughput. Next, a detailed classification of the routing strategies is given according to performance evaluation matrices which are considered according to specific demand and requirements of network users. A representative selection of these strategies is discussed in detail in this paper together with services given to unique challenges of CRN. Important issues and future directions are also discussed, while highlighting the need of close coupling between interaction of network users and dynamic decision theories.