Medications development for drug addiction and other neuropsychiatric disorders

Drug addiction and abuse especially opiate and psychostimulant abuse is a national and global crisis. IBNtxA (3-iodobenzoyl naltrexamine) is a novel mu opioid receptor (MOR) agonist, a naloxone derivative, structurally related to the classical MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, producing a unique pharmacological profile resulting in potent analgesia with reduced side effects. It has been found that M. vaccae has immunoregulatory effects that can prevent stress-induced exaggeration of neuroinflammation in the brain. The purpose of our pilot study is to develop medication for addiction and neuropsychiatric disorders. According to our purpose, we evaluated a range of IBNtxA doses to more fully assess its abuse liability and antiaddiction properties and the preimmunization effect of heat-killed M. vaccae on cocaine addiction. IBNtxA represents an intriguing lead compound for preclinical drug development specifically targeting MOR splice variants, potentially creating effective analgesics with reduced side effects. Furthermore, IBNtxA could have use as an adjunct therapy in agonist replacement strategies (e.g., methadone). M. vaccae might be helpful for cocaine relapse. Current collaborative efforts are aimed to find the total signaling pathways of IBNtxA and the effect of M. vaccae on cocaine self-administration, cocaine induced neuroinflammations and to keep finding medicine for neurological diseases

Study on baseline characteristics and lipid profile abnormalities among type 2 diabetic patients attending urban diabetic care hospital, Bangladesh

Background: Altered levels of serum glycated hemoglobin (HbA1c) and lipid profile are prevalent in patients having type 2 diabetic mellitus (T2DM). Aim of the study was to investigate the relationship between serum HbA1c and lipid profile in T2DM to predict diabetic dyslipidemia.Methods: A structured questionnaire was filled up by each study subject to collect data according to study protocol including age, gender, BMI, BP, residential status, socio-economic status, educational status, physical activity, dietary habit, smoking and duration of diabetes. We collected blood samples from 270 type-2 diabetes mellitus (T2DM) patients aged 30-65 years after overnight fasting (10-12 hours). Then blood samples collected from T2DM patients were used to measure serum levels of HbA1c, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were estimated by standard laboratory methods.Results: In this study, increased levels of fasting blood glucose (8.61 mmo/l), HbA1c (7.86%), TC (226.15 mg/dl), TG (193.34 mg/dl) and LDL (147.37 mg/dl), and decreased levels of HDL (40.36 mg/dl) were observed in T2DM patients. Moreover, the strong positive correlation of HbA1c levels with FBG, TC, TG, and LDL levels were found in this study. Besides, a very strong and significant negative correlation (R2=0.1822) between the serum levels of HbA1c and HDL were noted in this study.Conclusions: This study revealed a strong correlation between dyslipidemia and serum levels of HbA1c in T2DM patients

Crustal Structures of Diebold Knoll and Adjacent Juan De Fuca Oceanic Crust from Integration of Seismic, Gravity and Magnetic Data

Cascadia Subduction Zone (CSZ) has a long history of devastating earthquakes as the Juan de Fuca plate subducts beneath North America, where an imminent megathrust earthquake is expected. Compared to other subduction zones, CSZ exhibits unusually low seismic activity, particularly in the central region with respect to relatively high seismicity zones to the north and south. Some researchers attribute this behavior to subducted seamounts, although their impact on seismicity remains poorly understood and highly debated in the literature. Examining subducted seamounts is challenging due to complexity of the overburden strata. That is why this study focuses on an isolated not-yet-subducted intraplate seamount known as the Diebold Knoll, located approximately 60 km west of the deformation front. Seismic reflection, gravity, and magnetic data were acquired over that seamount during the cruise RR1718. The first objective of this research was to determine heterogeneities in physical properties of oceanic crust resulted from addition of the seamount by integrated geophysical analysis along two intersecting profiles. The second objective was to reveal the tectonic history of the Diebold Knoll by combining magnetic polarity reversals with cross-cutting relationship analysis of seismic structures and constrained by the nearby ocean drilling sites. These models revealed that Diebold Knoll does not require complete isostatic compensation. Instead, a flat Moho or a less than 1 km thick root is sufficient to satisfy gravity data; both of these Moho geometries are observed in the study area. To achieve a better fit with observed gravity and magnetic anomalies, lower density and magnetic susceptibility values within the top portion of the seamount are required, which are attributed to faulting and hydration. This finding is also in agreement with a recent study that analyzed seismic velocity variations within seamounts. Furthermore, the negative magnetic anomaly of the seamount and the cross-cutting relationships between sedimentary layers and the seamount body indicated that Diebold Knoll is a very young feature formed approximately 0.8-1.8 Ma. Advisor: Irina Filin

Investigating Monga

Food insecurity and poverty are interlinked and the main reason for migration in poor households from the northern part of Bangladesh. Individuals from poor households migrate in the hope of improving self-well-being and for their families. Monga-seasonal food insecurity is a multi-dimensional issue in the northern region of Bangladesh. The purpose of this study is to understand the adaptation strategies by the northern region people of Bangladesh against Monga-seasonal food insecurity. A qualitative approach has been used in this study and to assess the functionality of strategies for adaptation by the char dwellers in Rangpur against Monga-seasonal food insecurity has followed Talcott Parsons and his so-called AGIL system

Porcine Alveolar Macrophage Responses to Gram-positive and Gram-negative Bacterial Components in Innate Immunity

Alveolar macrophages (AMs) are important in the regulation of innate immune responses in the lung through their phagocytosis and the production of a variety of compounds, like cytokines and nitric oxide (NO). Newborn animals are known to manifest increased susceptibility to pulmonary infection, and thus we hypothesize that this may due in part to a deficiency in the function of AMs. To dissect the age-related immune responses, AMs were isolated from 5 (newborn), 40 (post-weaned) and 120 (young) day old pigs, and stimulated with lipopolysaccharide (LPS). Cytokine mRNA and protein was assayed by quantitative real-time PCR and ELISA, respectively. We report here that AM cells were relatively less abundant in broncho-alveolar lavage fluid in newborn piglets and their phagocytic capacity to Escherichia coli was lower than those of young pigs (P<0.05). LPS inducible mRNA for TLR-4, LBP, CD-14 and MyD-88 had higher expression in newborn piglets compared with those of young pigs (P<0.05) in a time-dependent manner. The kinetics results showed that AMs from newborn piglets were significantly less capable of producing IL1-β, IL-6, IL-12β, TNF-α, IL-8 and GM-CSF than post-weaned piglets or young pigs. In contrast, IL-10 was significantly higher in newborn piglets. The reasons for differences in cytokine production may reflect maturation of immune cells which indicate functional differences of cell population and may underlay the enhanced susceptibility of early born animals to pulmonary infections. Only very low levels of NO were detected in young pigs. Future investigations in more animals and across a wider age range are recommended. Furthermore, in another study, AMs were incubated for 24 h with various concentrations of LPS, lipoteichoic acid (LTA), LPS plus LTA or control. Overall, compared to LPS, LTA was a relatively weak inducer in releasing cytokines in a dose-dependent manner. Co-stimulation augmented TLR-2, CD-14 and MyD-88 mRNA, and subsequently produced elevated levels of IL-6, TNF-α and IL-8 when compared to LPS and LTA alone. Additionally, phagocytosis of macrophages was significantly increased following low concentration of LPS treatment. Collectively, our data suggest that during pulmonary infections, an exacerbated inflammatory response may occur inducing the enhanced release of cytokines. The mechanism underlying the synergistic up-regulation of TLRs-associated genes and inflammatory cytokines by combined stimulation is of concern

Unconstitutional Constitutional Amendments in South Asia: A Study of Constitutional Limits on Parliaments’ Amending Power

Against the backdrop of the landscape of Parliamentary Supremacy of south asian countries, members of parliament often cross their limit by thinking parliament as a sovereign body to make unnecessary constitutional amendments which are ultimately questioned by the courts. As a member of the legislative department, I unmasked the reasons behind this unauthorized exercise of power to stop the mockery of parliamentary democracy.Supreme Courts in south Asia are often asked to judge constitutionality of constitutional amendments which provides them with  the opportunity to engage with the noble issue of ‘constitutional limits on parliamentary amending power’. Constitutional courts and commentators have always recognized some short of constitutional limits on parliament’s power to amend the constitution, though the nature and scope of such limits have been a matter of controversy. Courts in South Asia are divided in their opinion. While Court in Bangladesh and India invoked implied substantive constitution limits in parliamentary amending power and declared constitutional amendment unconstitutional in number of occasions, Courts in Srilanka and Pakistan have refused to do so. This study aims to examine the extent and nature of constitutional limits on parliamentary amending power with reference to the constitutional amendments, if any, so far declared by the constitutional courts in South Asia. However, for space constraint and other limits, we will confine ourselves to considering only the constitutional amendments, if any, so far declared unconstitutional in India Pakistan and Bangladesh.  For the purpose this study, we will rely heavily on the jurisprudence developed by the Supreme Courts of Pakistan, India and Bangladesh in amendment cases, and on some fascinating academic literatures written by various constitutional commentators which directly address the position of the courts in these cases.Instead of discussing all the constitutional amendment cases in fragment, this paper will concentrate on studying various constitutional limits invoked by the courts on parliamentary amending power and opinions of the courts in those amendment cases will be referred in cases they are necessary in theoretical discussion of various constitutional limits. However, we will not go to see the procedural limits on amending power prescribed by the constitution itself, in that such limits being expressed in the provisions of the constitution are less controversial and does not merit much theoretical discussion. An attempt will be made to conceptualize the very concept of ‘unconstitutional constitutional amendment’. In this section we will look how the concept emerged in the jurisdictions beyond South Asia. Then will turn to see how South Asian courts in constitutional amendment cases have understood the concept. Conceptualizing unconstitutional constitutional amendment, we will turn to see the constitutional limits which are generally imposed on parliamentary amending power. In this regard, our focus will be to see various substantive constitutional limits invoked by the courts in India, Pakistan and Bangladesh. However details of such limits will be discussed in other appropriate sections dedicated for that purpose.Will have a short discussion on the definition of the term ‘amendment’ and examine if there is any limitation inherent in the term. It will be shown examination of the meaning of the term has greater importance in determining the scope of parliamentary amending power, as the court relied heavily in amendment cases on definition of the term to reach their conclusion.  Examination of the positions of the courts in this regard will show that there are some inherent limits in the term ‘amendment’ which will considerably limit the power of parliament to amend the constitution. In next section, limit on amending the basic features of the constitution will be discussed. The doctrine of basic structure doctrine will be examined as it is invoked by the courts in India, Bangladesh and Pakistan. A part will be dedicated to address some core criticisms which basic structure doctrine is often to face. At last part of the section, we will turn to see to what extent basic structure provisions are immuned form amendment.We will examine the level of entrenchment enjoyed by fundamental rights against constitutional amendment. Firstly, position of the courts regarding the question- whether fundamental rights are law for the purpose of fundamental rights review- will be examined. Then attempt will be made to see what extent fundamental rights provisions are immured from amendment as one of the basic features of the constitution.In later section we will consider the limit, invoked by the courts in basic structure cases, on radical change of the constitution so that constitutional identity and purpose are not lost. A brief discussion of the concept of constitutional identity with its components will be given in this section.Legitimacy of the constitutional limits on amending power will be considered in the light of various constitutional theories such as constitutionalism, democracy, sovereignty, parliamentary sovereignty and popular sovereignty. While the limits will be judged in the lights of some fundamental constitutional and political concepts, focus will be placed to see how the constitutional limits on constitutional amendment challenged theses theories and to what extent we are forced to rethink those principle or concepts. .We then will turn to see ‘what the constitution is’ and how scope of amendment invariably depends on how one take the constitution to be.  It will be seen that difference in views of the judges regarding nature of constitution ultimately leads them to vary in their positions as to constitutional limits on parliamentary amending power.  In the last section we will turn into the interpretative attitudes adopted by the court to support their position as regard constitutional limits. It is because, without examining the mode of interpretation which helps to base the limitations and the theories which support and contradict such limitation, nature and extent of the limits cannot be understood properly. Keywords: Parliament, Unconstitutional, Amendment, Supreme Cour

Mapping of Velocity Variations to Investigate Seismicity in the Upper Crust of the Central Virginia Seismic Zone, Virginia, USA

Local earthquake tomography is used to investigate three dimensional velocity structure in the aftershock zone of the 2011 Mineral, VA, mainshock. A total of 5125 arrival times for 324 aftershocks recorded by 12 stations were used in the inversion. The inversion volume is small (22 x 20 x 16 km) with a block size of 1 x 1 x 1 km. Most of the aftershocks located at or below 2 km are associated with an NE trending, SE dipping anomalous velocity region with negative P-wave velocity (Vp) anomalies, positive S-wave velocity (Vs) anomalies, and Vp/Vs ratios as low as 1.54. We interpret the anomalous region as a highly quartz-rich sandstone or quartzite that accumulated in Paleozoic time along the passive margin of Laurentia and subsequently incorporated into the Piedmont Chopawamsic terrane during the Taconic orogeny. Two negative Vp and Vs anomalies are interpreted as metagraywacke and typical Chopawamsic rocks

Kinetics of Length Scale Dependent Deformation of Gold Microspheres and Micropillars

In this thesis length and time scale dependence of the operative plastic deformation mechanisms in Au is studied. Uniaxial compression tests were performed at various loading rates on FIB-milled Au micropillars and single-crystalline Au microspheres of diameter ranging from 0.8 to 6.0 µm to investigate the incipient and bulk plasticity events. Constant-load ambient-temperature creep tests were performed on the micropillars to study the time-dependent plasticity at very slow strain rates. Uniaxial compression tests were also performed on coated Au microspheres to study the effect of extrinsic constraint on the deformation mechanisms. During uniaxial compression, both the Au micropillars and microspheres displayed strain jumps, the frequency of which decreased with increasing sample diameter and increasing resolved shear stress. The bulk flow stress, corresponding to 5% – 20% average compressive strain, was dependent upon both the strain rate and the specimen diameter. Analysis of the apparent activation volume, V*, and energy, Q*, of the deformation process indicated that the operative deformation mechanism for the small 0.8 µm diameter pillars and spheres was characteristic of a mechanism limited by surface nucleation of dislocations while larger diameter samples displayed values indicative of the more common dislocation-obstacle interaction limited deformation mechanism. The deformation-rate dependence of incipient plastic deformation of the Au micropillars and microspheres was also dependent upon the strain rate and sample diameter. For the smallest, sub-micrometer size, samples the incipient plasticity was controlled by heterogeneous dislocation nucleation events, while a dislocation-obstacle interaction limited glide process was found to be operative in the larger specimens. In the extrinsic constraint study, Au microspheres that were coated with a 40 – 80 nm thick Ni layer displayed a slightly increased flow stress compared to similar size uncoated microspheres. The estimated V* and Q* values for the coated microspheres suggest that the mechanism responsible for the initiation of first dislocation motion is essentially the same regardless of the presence of a constraining coating