Endometriosis Gene Expression Heterogeneity and Biosignature: A Phylogenetic Analysis

Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures

Dental Age In Kelantanese Malay Population Based On Demirjian's Method

Umur gigi amat penting untuk menganggarkan umur seseorang individu yang belum dewasa, membantu pakar pergigian pediatrik dan pakar ortodontik merancang pelan rawatan yang betul dan membuat penilaian perkembangan tahap gigi untuk sesuatu masalah perubatan. Dental age has a great importance in age estimation for non-adult individuals, helping the paediatric dentists and orthodontists to produce proper treatment plan, and assessment of the dental developmental level of certain medical conditions

Four Essays on Monetary Regimes: Inflation Targeting and a Fixed Exchange Rate system in Emerging Market Economies

Recent evidence has shown that monetary policy has a neutral real effect in the long run. Exploiting the short-run trade-off between inflation and unemployment creates an inflation bias which can be eliminated at a high economic and social cost. Hence, the only variable that could be controlled by the monetary authority in the long run is the inflation rate. This indicates that the monetary policy's role should be placed on achieving the goal of price stability. This thesis considers two monetary regimes with a quantitative target for the goal of price stability. It consists of four separate yet related empirical studies on inflation targeting and a fixed exchange rate system. First, we assess the institutional preconditions for adopting inflation targeting: central bank independence and transparency, in Jordan, where the credibility of low inflation is imported from abroad. These institutional requirements are assessed based on the experience of two inflation targeters that act as a benchmark of the study: New Zealand and the UK, in their first year of implementing the framework. The chapter addresses the institutional challenges of adopting inflation targeting when a country faces a macroeconomic trilemma of exchange rate stabilisation. The assessment of central bank independence, using the index of Mathew (2003), indicates that the central bank of Jordan is not independent as stated by the central bank's personal legislations. The central bank is also not fiscally independent; non-securitised and securitised lending is offered at no cost to cover the expenditure of the central government as well as the public corporations. The assessment of central bank transparency using the index of Eijffinger and Geraats (2006) shows that although providing the market with more transparent policies will not be infeasible, given the enhancement in the level of central bank independence, the central bank should clarify the policy changes and any inclination of preferences and release all relevant macroeconomic data to the public. Comparing the overall results to the two inflation targeters, the study recommends the need to grant the central bank more personal independence and induce more fiscal discipline which entails non-moneterisation of the government deficit in order to build a domestic reputation for the goal of price stability. Second, the interest rate pass through is examined within its intermediate lag of action to shed light on the credibility of monetary policy in Jordan, where the reputation of low inflation is imported through a fixed exchange rate system to the U.S dollar. The Johansen approach is performed to estimate the long-run degree of pass-through along with the speed of adjustment to disequilibrium. The parsimonious conditional dynamic model of Hendry and Doornik (1994) is employed to connect the short-run and long-run effect, and to estimate the mean lag of adjustment under (a)symmetric market response. The results are compared to that of two inflation targeting countries at time proceeding building the credibility of price stability domestically: New Zealand and the UK. This is to show how far Jordan is from building a domestic reputation for the goal of price stability. The empirical findings suggest that the interest rate pass-through in Jordan is weak and slow and the symmetric mean lags in the loan and deposit market are highly sticky. In addition, a deviation from symmetry is found in the loan market, where the mean lag is sticker to decreasing, which indicates the existence of non-competitive pricing behaviour in the market. Comparing the results to the two inflation targeters, the study suggests that Jordan needs to move to a more resilient exchange rate arrangement, provided the need for an intensive reform in economic constitutions and institutions. Third, we examine the credibility of the current experience of a pegged exchange rate system to the US dollar in eleven emerging market economies: Bahamas, Bahrain, Barbados, Belize, Egypt, Jordan, Oman, Kuwait, Lebanon, Qatar and Venezuela, over the annual span from 1996 to 2012. Based on the first generation-demand mismanagement models, the second generation of currency crises and the empirical works on the European Monetary System crisis, two proxies reflecting the market agents' realignment expectations are employed: the interest rate differential and the exchange rate market pressure index. The two proxies are regressed on a set of macro-fundamentals derived from the theory and empirical work of currency crises and gathered from the IMF-IFS and the World Bank Indicators. The analysis is based on unbalanced panel data models: fixed effects and first difference GMM. We construct different setups to consider the small sample size at hand and the nexus between current account and money stock as in the notion implied by the monetary approach to balance of payments, in which a balance of payments deficit results from excessive domestic credit creation. When interest rate differential is used as a proxy for the credibility, both panel models provide evidence that inflation differential is the main driving force for generating realignment expectations, and explains why anchoring interest rates in not feasible for soft fixed exchange rate targeting countries. This result is consistent with the empirical findings on the credibility of the European Monetary System before the collapse. However, when the exchange rate market pressure index is used as a proxy for the credibility, none of the fundamentals appear significant in explaining the realignment expectations. When we examine the credibility in the countries which have not experienced a shift in monetary regime during the study period: Bahamas, Bahrain, Barbados, Belize, Jordan, Oman, the estimation of the fixed effects model suggests that inflation differential is a vital factor of the credibility. The deterioration in current account and the reserve adequacy also appear to be important indicators for expecting realignment from the parity condition in these countries. Fourth, we investigate the relationship between inflation and inflation uncertainty under inflation targeting and a fixed exchange rate system and examine the role of both regimes in lowering inflation rate and inflation uncertainty. We utilise monthly data on consumer price index obtained from the IMF-IFS for the period 01:1980-06:2014 and construct different GARCH in mean models. The findings suggest that the hypotheses of Cukierman and Meltzer (1986) and Friedman (1977) and Ball et al. (1990) are valid under the two monetary regimes, that is, inflation uncertainty increases inflation and inflation generates inflation uncertainty, respectively. The results provide evidence that both regimes could reduce inflation uncertainty; however, it could be argued that the impact of exchange rate targeting on inflation uncertainty holds as long as the possibility to renege on the fixed parity commitment is not perceived by the market. The results also indicate that inflation targeters have been successful at reducing the inflation rate and inflation persistence more than fixed exchange rate targeting countries, where the regime has no impact on lowering average inflation and inflation inertia

Algorithmic Assessment of Vaccine-Induced Selective Pressure and Its Implications on Future Vaccine Candidates

Posttrial assessment of a vaccine's selective pressure on infecting strains may be realized through a bioinformatic tool such as parsimony phylogenetic analysis. Following a failed gonococcal pilus vaccine trial of Neisseria gonorrhoeae, we conducted a phylogenetic analysis of pilin DNA and predicted peptide sequences from clinical isolates to assess the extent of the vaccine's effect on the type of field strains that the volunteers contracted. Amplified pilin DNA sequences from infected vaccinees, placebo recipients, and vaccine specimens were phylogenetically analyzed. Cladograms show that the vaccine peptides have diverged substantially from their paternal isolate by clustering distantly from each other. Pilin genes of the field clinical isolates were heterogeneous, and their peptides produced clades comprised of vaccinated and placebo recipients' strains indicating that the pilus vaccine did not exert any significant selective pressure on gonorrhea field strains. Furthermore, sequences of the semivariable and hypervariable regions pointed out heterotachous rates of mutation and substitution

Inflation targeting or Exchange Rate Targeting: Which Framework Supports The Goal of Price Stability in Emerging Market Economics?

We investigate the relationship between inflation and inflation uncertainty under inflation targeting and a conventional fixed exchange rate system and the impact of each regime on inflation and inflation uncertainty over the span from 1980:01 to 2014:06. The results from GARCH in mean models reveal that, under the two monetary regimes, inflation increases inflation uncertainty and inflation uncertainty raises inflation. This positive bi-directional relationship between inflation and inflation uncertainty provides evidence of the importance of non-discretionary monetary policies. Both regimes appear effective in reducing inflation uncertainty in the long-run which suggests the importance of monetary regimes as signalling devices for inflation expectations. The fixed exchange rate regime has no impact on average inflation and inflation inertia, while inflation targeting has been successful at lowering average inflation and inflation persistence of its followers. Nevertheless, the results provide evidence that inflation targeting countries have not benefited equally from inflation targeting

Fabrication and Characterization of Fast-Dissolving Films Containing Escitalopram/Quetiapine for the Treatment of Major Depressive Disorder

Major depressive disorder (MMD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD fail to achieve response or remission leading to treatment-resistant depression (TRD). One of the psychopharmacological strategies to overcome TRD is using a combination of an antipsychotic as an augmenting agent with selective serotonin reuptake inhibitors (SSRIs). Among which, an atypical antipsychotic, quetiapine (QUE), and an SSRI, escitalopram (ESC), were formulated as a fixed-dose combination as a fast-dissolving film by coaxial electrospinning. The resultant fiber’s morphology was studied. SEM images showed that the drug-loaded fibers were smooth, un-beaded, and non-porous with a fiber diameter of 0.9 ± 0.1 µm, while the TEM images illustrated the distinctive layers of the core and shell, confirming the successful preparation of these fibers. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies confirmed that both drugs were amorphously distributed within the drug-loaded fibers. The drug-loaded fibers exhibited a disintegration time of 2 s, which accelerated the release of both drugs (50% after 5 min) making it an attractive formulation for oral mucosal delivery. The ex vivo permeability study demonstrated that QUE was permeated through the buccal membrane, but not ESC that might be hindered by the buccal epithelium and the intercellular lipids. Overall, the developed coaxial fibers could be a potential buccal dosage form that could be attributed to higher acceptability and adherence among vulnerable patients, particularly mentally ill patients

A Systems Biology Interpretation of Array Comparative Genomic Hybridization (aCGH) Data through Phylogenetics

Array Comparative Genomic Hybridization (aCGH) is a rapid screening technique to detect gene deletions and duplications, providing an overview of chromosomal aberrations throughout the entire genome of a tumor, without the need for cell culturing. However, the heterogeneity of aCGH data obfuscates existing methods of data analysis. Analysis of aCGH data from a systems biology perspective or in the context of total aberrations is largely absent in the published literature. We present here a novel alternative to the functional analysis of aCGH data using the phylogenetic paradigm that is well-suited to high dimensional datasets of heterogeneous nature, but has not been widely adapted to aCGH data. Maximum parsimony phylogenetic analysis sorts out genetic data through the simplest presentation of the data on a cladogram, a graphical evolutionary tree, thus providing a powerful and efficient method for aCGH data analysis. For example, the cladogram models the multiphasic changes in the cancer genome and identifies shared early mutations in the disease progression, providing a simple yet powerful means of aCGH data interpretation. As such, applying maximum parsimony phylogenetic analysis to aCGH results allows for the differentiation between drivers and passenger genes aberrations in cancer specimens. In addition to offering a novel methodology to analyze aCGH results, we present here a crucial software suite that we wrote to carry out the analysis. In a broader context, we wish to underscore that phylogenetic analysis of aCGH data is a non-parametric method that circumvents the pitfalls and frustrations of standard analytical techniques that rely on parametric statistics. Organizing the data in a cladogram as explained in this research article provides insights into the disease common aberrations, as well as the disease subtypes and their shared aberrations (the synapomorphies) of each subtype. Hence, we report the method and make the software suite publicly and freely available at http://software.phylomcs.com so that researchers can test alternative and innovative approaches to the analysis of aCGH data

Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy

BACKGROUND: Autophagy (macroautophagy), a cellular process of “self-eating”, segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin(s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes. FINDINGS: Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy. CONCLUSIONS: With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome