24 research outputs found
In Vitro Models of GJB2-Related Hearing Loss Recapitulate Ca2+ Transients via a Gap Junction Characteristic of Developing Cochlea
No full textSummaryMutation of the Gap Junction Beta 2 gene (GJB2) encoding connexin 26 (CX26) is the most frequent cause of hereditary deafness worldwide and accounts for up to 50% of non-syndromic sensorineural hearing loss cases in some populations. Therefore, cochlear CX26-gap junction plaque (GJP)-forming cells such as cochlear supporting cells are thought to be the most important therapeutic target for the treatment of hereditary deafness. The differentiation of pluripotent stem cells into cochlear CX26-GJP-forming cells has not been reported. Here, we detail the development of a novel strategy to differentiate induced pluripotent stem cells into functional CX26-GJP-forming cells that exhibit spontaneous ATP- and hemichannel-mediated Ca2+ transients typical of the developing cochlea. Furthermore, these cells from CX26-deficient mice recapitulated the drastic disruption of GJPs, the primary pathology of GJB2-related hearing loss. These in vitro models should be useful for establishing inner-ear cell therapies and drug screening that target GJB2-related hearing loss
A program evaluation of the Georgia justice project's employment assistance program, 2004
No full textThis evaluation examines the Georgia Justice Project's (GJP) employment program. GJP has been assisting its clients since 1986. GJP is an unlikely mix of lawyers, social workers, and a landscaping company. The Georgia Justice Project defends people accused of crimes and, win or lose, they stand by their clients while they rebuild their lives. GJP's mission is to ensure justice for the indigent criminally accused and to take a holistic approach to assisting them in establishing crime-free lives as productive citizens. GJP's goal is to have a positive impact on the lives of individual clients and their families, which in turn positively impacts the community by decreasing crime and violence. Helping clients rebuild their lives often involves helping them obtain employment. In 1993, New Horizon Landscaping Company was created to assist clients with employment needs. The services the employment program provides include job readiness, job placement, training, and GED preparation. These services help clients remove/overcome barriers (i.e., legal case, criminal record). The sample consists of sixty individuals who received assistance in 2002. The social services intake form was utilized to gather the information needed for the evaluation. The data was obtained by assessing each client's case file records. The following questions were addressed in this evaluation: (1) What were the employment needs presented by the program's clients? (2) What specific needs were met by existing services? (3) What needs were not being addressed? The data were collected by the researcher and interpreted for data analysis. The findings from this evaluation were expected to increase awareness when working with ex-offenders in the field of social work. The results of the evaluation and implications are discussed in later chapters
Crafting Coherent Policy Responses to the Crisis in the Philippines
No full textThe onslaught of the global economic crisis has thrown many workers in different parts of the world out of their jobs and many in the developing economies have fallen into situations of poverty. In search for the proper response to the crisis, various governments have turned to stimulus spending as a strategy to preserve and create jobs for their affected citizenry. The ILO tripartite constituents – government, workers and employers – designed a Global Jobs Pact (GJP) during the International Labour Conference in 2009. The GJP serves as a guiding framework to national and international policies aimed at stimulating economic recovery, generating jobs and providing protection to working people and their families. It seeks to promote a job-intensive recovery from the crisis. The Pact is built around the principles of the ILO’s Decent Work agenda. It looks at the issues of employment generation and sustainable enterprises. It emphasizes the need for a basic social protection floor. It calls attention to the importance of protecting and promoting rights at work in a crisis situation. It encourages the practice of social dialogue and collective bargaining as critical tools to identify priorities and assist in policy design and implementation. It calls for implementing measures quickly in a coordinated manner, and for integrating gender concerns throughout. The GJP is the response of the ILO and its tripartite constituency to the global crisis. The Pact contains a package of crisis-response and recovery measures. It is not a one-size-fitsall solution, but a portfolio of policy options that countries can adapt to their specific needs and situation. Indeed, a coherent and credible agenda for a rich-job recovery can only result from an in-depth national policy debate and consultation among policy makers and key stakeholders. Since 2001, the Philippines has adopted the Decent Work Common Agenda outlining projects and activities that will help workers, employers and government, achieve the major objectives of Decent Work. The current global crisis could be seen as an opportunity to craft stronger short term and long term responses that can incorporate key elements from the framework of the Global Jobs Pact and help the country restore viable economic growth, employment generation and poverty eradication
Strength influencing parameters of iroko glued laminated timber
No full textAs timber is being used for several millennia as construction material, glued laminated timber (glulam), a highly engineered timber product, exists for about hundred and fifty years. In Europe, it is nowadays common practise to make glulam from softwood species, though in the last few decades glulam made from different kinds of hardwoods emerged. Iroko glulam is part of this development, as iroko is a hardwood species from the African tropical regions. The aim of this thesis is to investigate the bending strength of iroko glulam, as well as strength influencing features. From literature it is expected that the following features are of influence: density, modulus of elasticity, tension strength of the lamellas, finger joint strength and size. Several researches conducted in the past experiments to determine these mechanical and physical properties, focusing mainly on iroko sawn timber. Only few investigated iroko glulam, and none of those focused on finger jointed iroko glulam. In this lies the originality of this work: determining bending strength values of finger jointed iroko glulam, as well as density, modulus of elasticity and investigating mechanical and physical properties of the base material: iroko sawn timber and iroko finger joints. The laboratory experiments included the following: tension tests on 38 unjointed and 38 finger jointed lamellas, and four point bending tests on 12 glulam beams. Also density, modulus of elasticity and moisture content were determined. The experimental results yield the following characteristic values: a lamella tension strength of 17 N/mm2, a finger joint tension strength of 29 N/mm2, and a glulam bending strength of 42 N/mm2 (including size effect according to NEN-EN 1995, 2011). The experimentally determined characteristic lamella tension strength is a little lower than values found in literature. This is due to a large scatter in the test results: a coefficient of variance equal to 0.37 was found. However, if the grain angle is equal or smaller than 5°, a higher lamella tension strength of 27 N/mm2 is feasible. Grain angle is as expected a significant strength influencing parameter for iroko sawn timber. And it would suggest that the strength class is as expected D40 if the lamella bending strength equals 0.6 divided by the lamella tension strength. The ratio of finger joint bending strength (30 N/mm2) and tension strength (29 N/mm2) on the characteristic level was found to be equal to 1.06. This is smaller than expected from theory: apparently the 1.4 ratio commonly assumed for softwood finger joint strength values does not hold for iroko finger joint strength values. The investigated iroko glulam beams with depth 108 mm yielded a mean bending strength of 66 N/mm2 and a characteristic bending strength of 42 N/mm2. Due to the size effect and quasi-brittle failure this figures lie lower for full scale glulam beams, however, strength class GL24h is indeed a safe assumption for iroko glulam beams. These aspects explain the higher mean glulam bending strength compared to the mean finger joint tension strength of 40 N/mm2. A strong mathematical relationship between characteristic glulam bending strength and both lamella tension strength and finger joint strength was not found; however lamella and finger joint tension strength do influence the glulam bending strength. Furthermore, density does not influence any strength or stiffness property for both iroko sawn timber, finger joints, and glulam beams. Although there is a slight positive correlation with both dynamic and local modulus of elasticity of lamellas and its tension strength.Civil Engineerin
Chromium(III) and chromium(IV) bis(trimethylsilyl) amido complexes as ethylene polymerisation catalysts
No full textOxidation of Cr[N(SiMe3)(2)](2)(THF)(2) with iodine and dicumyl peroxide results in tetrahedral Cr(IV)Cr[N(SiMe3)(2)](2)I-2 and trigonal planar Cr(III) Cr[N(SiMe3)(2)](OCMe2Ph)(2), respectively; both complexes have been characterised by single-crystal X-ray diffraction, and both are active for ethylene polymerisation with alkylaluminium co-catalysts.PT: J; CR: AJJOU JAN, 1997, ORGANOMETALLICS, V16, P86 AJJOU JAN, 2000, J AM CHEM SOC, V122, P8968 ALONSO PJ, 2002, CHEM-EUR J, V8, P4056 BASI JS, 1971, J CHEM SOC A, P1433 BEAUDOIN MC, 2002, J MOL CATAL A-CHEM, V190, P159 BERNO P, 1994, ORGANOMETALLICS, V13, P1052 BLANCHARD H, 1988, J ORGANOMET CHEM, V341, P367 BOCHMANN M, 1980, J CHEM SOC DA, P1863 BRADLEY DC, 1972, J CHEM SOC CHEM COMM, P567 BRADLEY DC, 1976, ACCOUNTS CHEM RES, V9, P273 BRADLEY DC, 1978, INORG SYNTH, V18, P112 BRITOVSEK GJP, 1999, ANGEW CHEM INT EDIT, V38, P428 BURGER H, 1964, MONATSH, V95, P1099 CUMMINS CC, 1992, ANGEW CHEM INT EDIT, V31, P1501 CUMMINS CC, 1998, PROG INORG CHEM, V47, P685 DRYKACZ G, 1973, J AM CHEM SOC, V95, P4756 ELLER PG, 1977, COORDIN CHEM REV, V24, P1 FILIPPOU AC, 2002, EUR J INORG CHEM NOV, P2928 FILIPPOU AC, 2003, ANGEW CHEM INT EDIT, V42, P4486 FILIPPOU AC, 2003, ORGANOMETALLICS, V22, P3010 FIRMAN TK, 2001, J ORGANOMET CHEM, V635, P153 FRYZUK MD, 1995, ORGANOMETALLICS, V14, P5193 GIBSON VC, 1998, CHEM COMMUN 0821, P1651 GIBSON VC, 1999, J CHEM SOC DALT 0321, P827 GIBSON VC, 2000, J CHEM SOC DALTON, P1969 GIBSON VC, 2001, EUR J INORG CHEM JUL, P1895 GIBSON VC, 2002, J CHEM SOC DALTON, P4017 GIBSON VC, 2003, CHEM REV, V103, P283 HAGIHARA N, 1959, J AM CHEM SOC, V81, P3160 IKEDA H, 2001, MACROMOL CHEM PHYSIC, V202, P1806 IKEDA H, 2002, J ORGANOMET CHEM, V642, P156 KAYAL A, 2002, INORG CHEM, V41, P321 LAPLAZA CE, 1996, J AM CHEM SOC, V118, P8623 MESSERE R, 2000, EUR J INORG CHEM JUN, P1151 MINDIOLA DJ, 1998, ANGEW CHEM INT EDIT, V37, P945 MOWAT W, 1972, J CHEM SOC DA, P533 MOWAT W, 1973, J CHEM SOC DA, P770 ROBERTSON NJ, 2003, INORG CHEM, V42, P6876 SCHMID R, 2000, CAN J CHEM, V78, P265 SCHMID R, 2000, ORGANOMETALLICS, V19, P2756 SCHNEIDER S, 2001, INORG CHEM, V40, P4674 SCHULZKE C, 2002, ORGANOMETALLICS, V21, P3810 SCOTT SL, 2001, CHEM ENG SCI, V56, P4155 SEIDEL W, 1976, Z ANORG ALLG CHEM, V426, P150 SEIDEL W, 1976, Z ANORG ALLG CHEM, V426, P155 SMALL BL, 2004, MACROMOLECULES, V37, P4375 THEOPOLD KH, 1998, EUR J INORG CHEM JAN, P15 VANRENSBURG WJ, 2004, ORGANOMETALLICS, V23, P1207; NR: 48; TC: 3; J9: DALTON TRANS; PG: 3; GA: 865WTSource type: Electronic(1
Purification, Characterization and Cdna Sequence of An Alkaline Chymotrypsin From the Midgut of Manduca-Sexta
No full textQuantification of functional abilities in Rett syndrome: a comparison between stages III and IV
No full textCarlos BM Monteiro,1 Geert JP Savelsbergh,2 Ana RP Smorenburg,3 Zodja Graciani,4 Camila Torriani-Pasin,5 Luiz Carlos de Abreu,6 Vitor E Valenti,7 Fernando Kok41School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil; 2MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University, Amsterdam, the Netherlands; 3Burke-Cornell Medical Research Institute, White Plains, NY, USA; 4Department of Neurology, University of São Paulo, São Paulo, Brazil; 5Motor Behavior Laboratory, University of São Paulo, São Paulo, Brazil; 6Laboratory of Scientific Writing, Department of Morphology and Physiology, School of Medicine of ABC, Santo Andre, Brazil; 7Department of Speech Language and Hearing Therapy, Faculty of Philosophy and Sciences, UNESP, Marilia, BrazilAbstract: We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric ­Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life.Keywords: Rett syndrome, disability evaluation, self-care, mobility limitatio
Complete protection by a single-dose skin patch-delivered SARS-CoV-2 spike vaccine.
No full textSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 160 million people and resulted in more than 3.3 million deaths, and despite the availability of multiple vaccines, the world still faces many challenges with their rollout. Here, we use the high-density microarray patch (HD-MAP) to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin. We show that the vaccine is thermostable on the patches, with patch delivery enhancing both cellular and antibody immune responses. Elicited antibodies potently neutralize clinically relevant isolates including the Alpha and Beta variants. Last, a single dose of HD-MAP–delivered spike provided complete protection from a lethal virus challenge in an ACE2-transgenic mouse model. Collectively, these data show that HD-MAP delivery of a SARS-CoV-2 vaccine was superior to traditional needle-and-syringe vaccination and may be a significant addition to the ongoing COVID-19 (coronavirus disease 2019) pandemic.Full Tex
The changing shape of vaccination: Improving immune responses through geometrical variations of a microdevice for immunization
No full textMicro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination
On the relation between action selection and movement control in 5- to 9-month-old infants.
No full textAlthough 5-month-old infants select action modes that are adaptive to the size of the object (i.e., one- or two-handed reaching), it has largely remained unclear whether infants of this age control the ensuing movement to the size of the object (i.e., scaling of the aperture between hands). We examined 5-, 7-, and 9-month-olds' reaching behaviors to gain more insight into the developmental changes occurring in the visual guidance of action mode selection and movement control, and the relationship between these processes. Infants were presented with a small set of objects (i.e., 2, 3, 7, and 8 cm) and a large set of objects (i.e., 6, 9, 12, and 15 cm). For the first set of objects, it was found that the infants more often performed two-handed reaches for the larger objects based on visual information alone (i.e., before making contact with the object), thus showing adaptive action mode selection relative to object size. Kinematical analyses of the two-handed reaches for the second set of objects revealed that inter-trial variance in aperture between the hands decreased with the approach toward the object, indicating that infants' reaching is constrained by the object. Subsequent analysis showed that between hand aperture scaled to object size, indicating that visual control of the movement is adjusted to object size in infants as young as 5 months. Individual analyses indicated that the two processes were not dependent and followed distinct developmental trajectories. That is, adaptive selection of an action mode was not a prerequisite for appropriate aperture scaling, and vice versa. These findings are consistent with the idea of two separate and independent visual systems (Milner and Goodale in Neuropsychologia 46:774-785, 2008) during early infancy. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201
