Dynamics of weakly coupled random antiferromagnetic quantum spin chains

We study the low-energy collective excitations and dynamical response functions of weakly coupled random antiferromagnetic spin-1/2 chains. The interchain coupling leads to Neel order at low temperatures. We use the real-space renormalization group technique to tackle the intrachain couplings and treat the interchain couplings within the Random Phase Approximation (RPA). We show that the system supports collective spin wave excitations, and calculate the spin wave velocity and spectra weight within RPA. Comparisons will be made with inelastic neutron scattering experiments quasi-one-dimensional disordered spin systems such as doped CuGeO$_3$Comment: 4 page

Emerging Roles of Glycogen Synthase Kinase 3 in the Treatment of Brain Tumors

The constitutively active protein glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, acts paradoxically as a tumor suppressor in some cancers while potentiates growth in others. Deciphering what governs its actions is vital for understanding many pathological conditions, including brain cancer. What are seemingly disparate roles of GSK3 stems from the complex regulation of many cellular functions by GSK3. This review focuses on the regulation of GSK3, its role in survival, apoptosis and DNA damage, and finally its potential therapeutic impact in brain cancer. A thorough understanding of this versatile protein is critical for improving the outcome of various diseases, especially cancer

Refractory lympho-epithelial carcinoma of the nasopharynx: a case report illustrating a protracted clinical course

Nasopharyngeal carcinoma is an uncommon cancer in North America. Its clinical course is typified by locally advanced disease at diagnosis and has a high propensity for both regional and distant spread. It is, therefore, typically treated with a combination of radiation and chemotherapy. This report describes our 10-year clinical and radiological findings in a 48-year-old Vietnamese male patient with locally-advanced T4N1M0 lympho-epithelial carcinoma of the nasopharynx. Despite a long remission period after his initial course of aggressive chemoradiation, his tumor recurred locally after 4 years. Thereafter, throughout a period of over 10 years, he has been treated with multiple courses of re-irradiation and three different trials of chemotherapy. He was ultimately provided with over 30 months of progression-free tumor control with the epidermal growth factor receptor (EGFR)-inhibitor cetuximab. This case illustrates the commonly protracted course of this disease and its responsiveness to multiple treatment modalities

Grand minima and maxima of solar activity: New observational constraints

Using a reconstruction of sunspot numbers stretching over multiple millennia, we analyze the statistics of the occurrence of grand minima and maxima and set new observational constraints on long-term solar and stellar dynamo models. We present an updated reconstruction of sunspot number over multiple millennia, from $^{14}$C data by means of a physics-based model, using an updated model of the evolution of the solar open magnetic flux. A list of grand minima and maxima of solar activity is presented for the Holocene (since 9500 BC) and the statistics of both the length of individual events as well as the waiting time between them are analyzed. The occurrence of grand minima/maxima is driven not by long-term cyclic variability, but by a stochastic/chaotic process. The waiting time distribution of the occurrence of grand minima/maxima deviates from an exponential distribution, implying that these events tend to cluster together with long event-free periods between the clusters. Two different types of grand minima are observed: short (30--90 years) minima of Maunder type and long ($>$110 years) minima of Sp\"orer type, implying that a deterministic behaviour of the dynamo during a grand minimum defines its length. The duration of grand maxima follows an exponential distribution, suggesting that the duration of a grand maximum is determined by a random process. These results set new observational constraints upon the long-term behaviour of the solar dynamo.Comment: 10 Figure

Random Antiferromagnetic Spin-1/2 Chains with Competing Interactions

We study disordered antiferromagnetic spin-1/2 chains with nearest- and further-neighbor interactions using the real-space renormalization-group method. We find that the system supports two different phases, depending on the ratio of the strength between nearest-neighbor and further-neighbor interactions as well the bond randomness strength. For weak further neighbor coupling the system is in the familiar random singlet phase, while stronger further neighbor coupling drives the system to a large spin phase similar to that found in the study of random antiferromagnetic-ferromagnetic spin chains. The appearance of the large spin phase in the absence of ferromagnetic coupling is due to the frustration introduced by further neighboring couplings, and is unique to the disordered chains.Comment: 11 pages, 7 figure

Genomic instability in human cancer: molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Lung cancer is the leading cause of cancer-associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane-associated protein myristoylated alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double-strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double-strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation. Keywords: lung cancer, myristoylated alanine rich C-kinase substrate, radiation sensitivity, effector domain, peptide mimeti

Towards Reliable Automatic Protein Structure Alignment

A variety of methods have been proposed for structure similarity calculation, which are called structure alignment or superposition. One major shortcoming in current structure alignment algorithms is in their inherent design, which is based on local structure similarity. In this work, we propose a method to incorporate global information in obtaining optimal alignments and superpositions. Our method, when applied to optimizing the TM-score and the GDT score, produces significantly better results than current state-of-the-art protein structure alignment tools. Specifically, if the highest TM-score found by TMalign is lower than (0.6) and the highest TM-score found by one of the tested methods is higher than (0.5), there is a probability of (42%) that TMalign failed to find TM-scores higher than (0.5), while the same probability is reduced to (2%) if our method is used. This could significantly improve the accuracy of fold detection if the cutoff TM-score of (0.5) is used. In addition, existing structure alignment algorithms focus on structure similarity alone and simply ignore other important similarities, such as sequence similarity. Our approach has the capacity to incorporate multiple similarities into the scoring function. Results show that sequence similarity aids in finding high quality protein structure alignments that are more consistent with eye-examined alignments in HOMSTRAD. Even when structure similarity itself fails to find alignments with any consistency with eye-examined alignments, our method remains capable of finding alignments highly similar to, or even identical to, eye-examined alignments.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Adjacent Nucleotide Dependence in ncRNA and Order-1 SCFG for ncRNA Identification

Background: Non-coding RNAs (ncRNAs) are known to be involved in many critical biological processes, and identification of ncRNAs is an important task in biological research. A popular software, Infernal, is the most successful prediction tool and exhibits high sensitivity. The application of Infernal has been mainly focused on small suspected regions. We tried to apply Infernal on a chromosome level; the results have high sensitivity, yet contain many false positives. Further enhancing Infernal for chromosome level or genome wide study is desirable. Methodology: Based on the conjecture that adjacent nucleotide dependence affects the stability of the secondary structure of an ncRNA, we first conduct a systematic study on human ncRNAs and find that adjacent nucleotide dependence in human ncRNA should be useful for identifying ncRNAs. We then incorporate this dependence in the SCFG model and develop a new order-1 SCFG model for identifying ncRNAs. Conclusions: With respect to our experiments on human chromosomes, the proposed new model can eliminate more than 50 % false positives reported by Infernal while maintaining the same sensitivity. The executable and the source code of programs are freely available a