Singing from the same hymn sheet? A closer look at the framing of human trafficing by counter-trafficing actors in Lao PDR

As disparities in wealth levels between and within countries become greater many poor people migrate in search of better earning opportunities. Some of this migration is legal but, in many cases, the difficulties involved in securing the necessary documentation mean that would-be migrants resort to illegal methods. This, in turn, makes them vulnerable to human trafficking, a phenomenon that has received growing attention from NGOs, governments and the media in recent years. Despite the attention being given to human trafficking, however, there remains a certain amount of confusion over what exactly it entails though it is generally understood to refer to the transportation and subsequent exploitation of vulnerable people through means of force or deception. The increased attention that has been given to the issue of human trafficking over the last decade has resulted in new discourses emerging which attempt to explain what human trafficking entails, what the root causes of the phenomenon are and how best to tackle the problem. While a certain degree of conceptual clarity has been attained since human trafficking rose to prominence in the 1990s, it could be argued that human trafficking remains a poorly defined concept and that there is frequently confusion concerning the difference between it and related concepts such as people smuggling, migration and prostitution. The thesis examines the ways in which human trafficking has been conceptualised or framed in a specific national context- that of Lao PDR. Attention is given to the task of locating the major frames within which the issue has been situated, as well as considering the diagnoses and prognoses that the various approaches to trafficking suggest. The research considers which particular strands of trafficking discourse have become dominant in Lao PDR and the effect this has had on the kinds of trafficking interventions that have been undertaken in the country. The research is mainly qualitative and consists of an analysis of key texts found in the Lao trafficking discourse.

Ability of human chorionic gonadotropin beta-subunit to inhibit the steroidogenic response to lutropin.

Ability of the beta-subunit of human chorionic gonadotropin to inhibit the response to lutropin (luteinizing hormone, LH) was tested in the immature rat ovarian system and pregnant-mare-serum-gonadotropin-primed rat ovarian system with progesterone production being used as the response. Human chorionic gonadotropin beta-subunit was found to inhibit human and ovine lutropin-stimulated progesterone production. At a constant dose of lutropin, inhibition was dependent on the concentration of beta-subunit. When concentration of the beta-subunit was kept constant at 5.0 microgram/ml and the concentration of lutropin was varied, the inhibition was maximum at the saturating concentration of the native hormone. The alpha-subunit of the human chorionic gonadotropin did not inhibit the response to lutropin. The lutropin/beta-subunit ratio required to produce an inhibition of response was much lower than that required to bring about an observable inhibition of binding.

The destabilization of human GCAP1 by a proline to leucine mutation might cause cone-rod dystrophy

Guanylate cyclase activating protein-1 (GCAP1) is required for activation of retinal guanylate cyclase-1 (RetGC1), which is essential for recovery of photoreceptor cells to the dark state. In this paper, experimentally derived observations are reported that help in explaining why a proline→leucine mutation at position 50 of human GCAP1 results in cone–rod dystrophy in a family carrying this mutation. The primary amino acid sequence of wild-type GCAP1 was mutated using site-directed mutagenesis to give a leucine at position 50. In addition, serine replaced a glutamic acid residue at position 6 to promote N‐terminal myristoylation, yielding the construct GCAP1 E6S/P50L. The enzyme was over-expressed in Escherichia coli cells, isolated and purified before being used in assays with RetGC1, characterized by circular dichroism (CD) spectroscopy, and investigated for protease resistance and thermal stability. Assays of cyclic guanosine monophosphate (cGMP) synthesis from guanosine triphosphate by RetGC1 in the presence of E6S/P50L showed that E6S/P50L could activate RetGC1 and displayed similar calcium sensitivity to wild-type GCAP1. In addition, E6S/P50L and wild-type GCAP1 possess similar CD spectra. However, there was a marked increase in the susceptibility to protease degradation and also a reduction in the thermal stability of E6S/P50L as observed by both the cGMP assay and CD spectroscopy. It is therefore suggested that although GCAP1 E6S/P50L has a similar activity and calcium dependency profile to the wild-type GCAP1, its lower stability could reduce its cellular concentration, which would in turn alter [Ca2+] and result in death of cells.

Antibodies against the extracellular domain of human Notch1 receptor reveal the critical role of epidermal-growth-factor-like repeats 25-26 in ligand binding and receptor activation

The Notch signalling pathway is implicated in a wide variety of cellular processes throughout metazoan development. Although the downstream mechanism of Notch signalling has been extensively studied, the details of its ligand-mediated receptor activation are not clearly understood. Although the role of Notch ELRs EGF (epidermal growth factor)-like-repeats] 11-12 in ligand binding is known, recent studies have suggested interactions within different ELRs of the Notch receptor whose significance remains to be understood. Here, we report critical inter-domain interactions between human Notch1 ELRs 21-30 and the ELRs 11-15 that are modulated by calcium. Surface plasmon resonance analysis revealed that the interaction between ELRs 21-30 and ELRs 11-15 is similar to 10-fold stronger than that between ELRs 11-15 and the ligands. Although there was no interaction between Notch 1 ELRs 21-30 and the ligands in vitro, addition of pre-clustered Jagged1Fc resulted in the dissociation of the preformed complex between ELRs 21-30 and 11-15, suggesting that inter-domain interactions compete for ligand binding. Furthermore, the antibodies against ELRs 21-30 inhibited ligand binding to the full-length Notch1 and subsequent receptor activation, with the antibodies against ELRs 25-26 being the most effective. These results suggest that the ELRs 25-26 represent a cryptic ligand-binding site which becomes exposed only upon the presence of the ligand. Thus, using specific antibodies against various domains of the Notch1 receptor, we demonstrate that, although ELRs 11-12 are the principal ligand-binding site, the ELRs 25-26 serve as a secondary binding site and play an important role in receptor activation.

Infection of human amniotic and endothelial cells by Japanese encephalitis virus: Increased expression of HLA-F

Productive infection of human amniotic and endothelial cell lines with Japanese encephalitis virus (JEV) was established leading to the induction of NF kappa B and HLA-F, a non-classical MHC molecule. Induction of the HLA-F gene and protein in JEV-infected cells was shown to be NF kappa B dependent since it was blocked by inhibitors of NF kappa B activation. ShRNA targeting lentivirus-mediated stable knockdown of the p65 subunit of NF kappa B inhibited JEV-mediated induction of HLA-F both in the amniotic cell line, AV-3 as well as the human brain microendothelial cell line, HBMEC. The induction of HLA-F by treatment of AV-3 with TNF-alpha was also inhibited by ShRNA mediated knockdown of NF kappa B. TNF-alpha treatment of HEK293T cells that were transfected with reporter plasmids under the control of HLA-F enhancer A elements resulted in significant transactivation of the luciferase reporter gene. NF kappa B-mediated induction of HLA-F following JEV infection and TNF-alpha exposure is being suggested for the first time. (C) 2014 Elsevier Inc. All rights reserved.

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long-term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15 and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs - LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. (C) 2015 The Authors. Published by Elsevier B.V.

Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation

CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by h

Study on the multiple sites binding of human serum albumin and porphyrin by affinity capillary electrophoresis

Equations to describe the two sites binding between proteins and ligands were deduced. According to these equations, not only the binding constants, but also the mole fraction of proteins in different forms could be obtained. Using the published data on the interaction between human serum albumin (HSA) and three kinds of porphyrin (coproporphyrin (CP), uroporphyrin I (UP) and protoporphyrin (PP)), a further study on their binding was carried out. It was concluded that there may exist two binding sites with the binding constants at the first site. proved to be the preferential one, being 6.50 x 10(5) 1.94 x 10(6) and 8.94 x 10(5). respectively. In addition. it was also demonstrated that the two binding sites of HSA with CP and UP might be of different kinds, though those of HSA and PP were of the same kind but at different positions. (C) 2002 Elsevier Science B.V. All rights reserved.

Computer modelling of human behaviour in aircraft fire accidents

The mathematical simulation of the evacuation process has a wide and largely untapped scope of application within the aircraft industry. The function of the mathematical model is to provide insight into complex behaviour by allowing designers, legislators, and investigators to ask ‘what if’ questions. Such a model, EXODUS, is currently under development, and this paper describes its evolution and potential applications. EXODUS is an egress model designed to simulate the evacuation of large numbers of individuals from an enclosure, such as an aircraft. The model tracks the trajectory of each individual as they make their way out of the enclosure or are overcome by fire hazards, such as heat and toxic gases. The software is expert system-based, the progressive motion and behaviour of each individual being determined by a set of heuristics or rules. EXODUS comprises five core interacting components: (i) the Movement Submodel — controls the physical movement of individual passengers from their current position to the most suitable neighbouring location; (ii) the Behaviour Submodel — determines an individual's response to the current prevailing situation; (iii) the Passenger Submodel — describes an individual as a collection of 22 defining attributes and variables; (iv) the Hazard Submodel — controls the atmospheric and physical environment; and (v) the Toxicity Submodel — determines the effects on an individual exposed to the fire products, heat, and narcotic gases through the Fractional Effective Dose calculations. These components are briefly described and their capabilities and limitations are demonstrated through comparison with experimental data and several hypothetical evacuation scenarios.

AASK - Aircraft accident statistics and knowledge: A database of human experience in evacuation, derived from aviation accident reports

Computer based mathematical models describing the aircraft evacuation process have a vital role to play in aviation safety. However such models have a heavy dependency on real evacuation data in order to (a) identify the key processes and factors associated with evacuation, (b) quantify variables and parameters associated with the identified factors/processes and finally (c) validate the models. The Fire Safety Engineering Group of the University of Greenwich is undertaking a large data extraction exercise from three major data sources in order to address these issues. This paper describes the extraction and application of data from one of these sources - aviation accident reports. To aid in the storage and analysis of the raw data, a computer database known as AASK (aircraft accident statistics and knowledge) is under development. AASK is being developed to store human observational and anecdotal data contained in accident reports and interview transcripts. AASK comprises four component sub-databases. These consist of the ACCIDENT (crash details), FLIGHT ATTENDANT (observations and actions of the flight attendants), FATALS (details concerning passenger fatalities) and PAX (observations and accounts from individual passengers) databases. AASK currently contains information from 25 survivable aviation accidents covering the period 4 April 1977 to 6 August 1995, involving some 2415 passengers, 2210 survivors, 205 fatalities and accounts from 669 people. In addition to aiding the development of aircraft evacuation models, AASK is also being used to challenge some of the myths which proliferate in the aviation safety industry such as, passenger exit selection during evacuation, nature and frequency of seat jumping, speed of passenger response and group dynamics. AASK can also be used to aid in the development of a more comprehensive approach to conducting post accident interviews, and will eventually be used to store the data directly.

An aircraft accident database of human experience in evacuation derived from aviation accident reports

Computer based mathematical models describing the aircraft evacuation process have a vital role to play in aviation safety. However, such models have a heavy dependency on real evacuation data. The Fire Safety Engineering Group of the University of Greenwich is undertaking a large data extraction exercise in order to address this issue. This paper describes the extraction and application of data from aviation accident reports. To aid in the storage and analysis of the raw data, a computer database known as AASK (Aircraft Accident Statistics and Knowledge) is under development. AASK is being developed to store human observational and anecdotal data contained in accident reports and interview transcripts. AASK currently contains information from 25 survivable aviation accidents covering the period 04/04/77 to 06/08/95, involving some 2415 passengers, 2210 survivors, 205 fatalities and accounts from 669 people. Copyright © 1999 John Wiley & Sons, Ltd.

An analysis of human behaviour during aircraft evacuation situations using the AASK v3.0 database

The Aircraft Accident Statistics and Knowledge (AASK) database is a repository of survivor accounts from aviation accidents. Its main purpose is to store observational and anecdotal data from the actual interviews of the occupants involved in aircraft accidents. The database has wide application to aviation safety analysis, being a source of factual data regarding the evacuation process. It is also key to the development of aircraft evacuation models such as airEXODUS, where insight into how people actually behave during evacuation from survivable aircraft crashes is required. This paper describes recent developments with the database leading to the development of AASK v3.0. These include significantly increasing the number of passenger accounts in the database, the introduction of cabin crew accounts, the introduction of fatality information, improved functionality through the seat plan viewer utility and improved ease of access to the database via the internet. In addition, the paper demonstrates the use of the database by investigating a number of important issues associated with aircraft evacuation. These include issues associated with social bonding and evacuation, the relationship between the number of crew and evacuation efficiency, frequency of exit/slide failures in accidents and exploring possible relationships between seating location and chances of survival. Finally, the passenger behavioural trends described in analysis undertaken with the earlier database are confirmed with the wider data set.

Impact of human activities on benthic biotopes and species

Executive Summary 1. The Marine Life Information Network (MarLIN) has been developed since 1998. Defra funding has supported a core part of its work, the Biology and Sensitivity Key Information Sub-programme. This report relates to Biology and Sensitivity work for the period 2001-2004. 2. MarLIN Biology and Sensitivity research takes information on the biology of species to identify the likely effects of changing environmental conditions linked to human activities on those species. In turn, species that are key functional, key structural, dominant, or characteristic in a biotope (the habitat and its associated species) are used to identify biotope sensitivity. Results are displayed over the World Wide Web and can be accessed via a range of search tools that make the information of relevance to environmental management. 3. The first Defra contract enabled the development of criteria and methods of research, database storage methods and the research of a wide range of species. A contract from English Nature and Scottish Natural Heritage enabled biotopes relevant to marine SACs to be researched. 4. Defra funding in 2001-2004 has especially enabled recent developments to be targeted for research. Those developments included the identification of threatened and declining species by the OSPAR Biodiversity Committee, the development of a new approach to defining sensitivity (part of the Review of Marine Nature Conservation), and the opportunity to use Geographical Information Systems (GIS) more effectively to link survey data to MarLIN assessments of sensitivity. 5. The MarLIN database has been developed to provide a resource to 'pick-and-mix' information depending on the questions being asked. Using GIS, survey data that provides locations for species and biotopes has been linked to information researched by MarLIN to map the likely sensitivity of an area to a specified factor. Projects undertaken for the Irish Sea pilot (marine landscapes), in collaboration with CEFAS (fishing impacts) and with the Countryside Council for Wales (oil spill response) have demonstrated the application of MarLIN information linked to survey data in answering, through maps, questions about likely impacts of human activities on seabed ecosystems. 6. GIS applications that use MarLIN sensitivity information give meaningful results when linked to localized and detailed survey information (lists of species and biotopes as point source or mapped extents). However, broad landscape units require further interpretation. 7. A new mapping tool (SEABED map) has been developed to display data on species distributions and survey data according to search terms that might be used by an environmental manager. 8. MarLIN outputs are best viewed on the Web site where the most up-to-date information from live databases is available. The MarLIN Web site receives about 1600 visits a day. 9. The MarLIN approach to assessing sensitivity and its application to environmental management were presented in papers at three international conferences during the current contract and a 'touchstone' paper is to be published in the peer-reviewed journal Hydrobiologia. The utility of MarLIN information for environmental managers, amongst other sorts of information, has been described in an article in Marine Pollution Bulletin. 10. MarLIN information is being used to inform the identification of potential indicator species for implementation of the Water Framework Directive including initiatives by ICES. 11. Non-Defra funding streams are supporting the updating of reviews and increasing the amount of peer review undertaken; both of which are important to the maintenance of the resource. However, whilst MarLIN information is sufficiently wide ranging to be used in an 'operational' way for marine environmental protection and management, new initiatives and the new biotopes classification have introduced additional species and biotopes that will need to be researched in the future. 12. By the end of the contract, the Biology and Sensitivity Key Information database contained full Key Information reviews on 152 priority species and 117 priority biotopes, together with basic information on 412 species; a total of 564 marine benthic species.

Cryopreservation of human semen and prepared sperm: effects on motility parameters and DNA integrity

Objective: To investigate effects of cryopreservation on sperm motility and DNA integrity. Design: Pre-cryopreservation and post-cryopreservation analysis of motility and DNA integrity of semen and prepared sperm samples. Setting: A hospital andrology laboratory. Patient(s): Forty men attending the Regional Fertility Centre, Belfast, Northern Ireland. Intervention(s): Each sample was divided, and an aliquot was frozen unprepared. Remaining aliquots were prepared by Percoll density centrifugation (95.0:47.5) or direct swim-up procedure and divided into aliquots to allow direct comparison of fresh and frozen semen and prepared sperm (frozen with or without the addition of seminal plasma) from the same ejaculate. Samples were frozen by static-phase vapor cooling and being plunged into liquid nitrogen. Thawing was carried out at room temperature. Main Outcome Measure(s): Sperm DNA integrity was determined using a modified alkaline single cell gel electrophoresis (comet) assay, and motility was determined using computer-assisted semen analysis. Result(s): Sperm frozen unprepared in seminal fluid appeared more resistant to freezing damage than frozen prepared sperm. Further improvements can be achieved by selecting out the subpopulation of sperm with best motility and DNA integrity and freezing these sperm in seminal plasma, making this the optimal procedure. Conclusion(s): Freezing sperm in seminal plasma improves postthaw motility and DNA integrity.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009