A Study of the Recidivism Rate of First Offenders at Louisiana Correctional and Industrial School Who Completed Vocational Training Through L.C.I.S./Sowela Institute

T h e p i.i. r p 0 s e o f\u27 t h e s t \u27J. d y w a. •=• t o d e t e r rn i n & i t 1 n m a t e s r e 1 e a. s e d +\u27 r c\u3e rn i_ o u i s i a n a C o r r e c t i o n a. 1 a n d Industrial School who completed a v o c a t i o n a 1 t r a i n i n 9 p r 0 9 r a rn t h r 0 u. 9 h L • C • I • S ■ S 0 w e l a T e c h n i c a 1 I n s t i t u t 0 h a d a 1 o w e r r a t e o f 0 f r e c i d i v i s rn t h a n t h 0 s e w h 0 d i d n ot c 0 rn p 1 e t e t r a i ti i ti 9 j u. s i n 9 a 9 e a s a v a r i a b 1 e ■ The population for this study consisted of a r a n d o rn s a rn pie o f\u27 99 i n rn a t es r e 1 e a se d i n t o t h e 9 e n e r a 1 p o p u 1 a t i 0 n 0 f\u27 L o u. i s i a n a p r i o r t o 1 9 S 3- T h e s e s u b ,i ec t s o 1 a n t a r i 1 y c o rn p 1 e t e d oc a. t i o n a 1 t r a 1 n i n9 i n in e 1 d i. n 9 ? a u t o m e c h a n i c s ? o r t\u3c 0 d y a n d f e n d e r repair betweeri the years 1376-1982 • The control s a rn p 1 e c o ns i s t e d 0f 101 i n rn a tes selects d r a n d o rn 1 y + rom the tot a1 p r i so n p op u 1 a t i on at L • C ■ I • S ■ dur i n9 19,-b- and who were released into the general P o p u 1 a t i o n o t L o u. i s i a ti a p r i o r t o 1983. Three years were a 110wed f\u270r the reci d ivism period- R e c i d i v i s rn w a s 0 p e r a t i 0 n a 1 i z e d a s r e t u r n 1 n 9 t o p r i s 0 fi o r o b t a i n i ti 9 a n e w f e 1 o n y \u3e_ h a r 9 e ? v e r i f\u27 i e d fc\u3e y Loij. i s i a na Dep- a.r t rne r 11 of Correc t i o ns dat a. a. nd the FBI c 0 rn p u t e r s y s t e rn. C h i - s q u. a re t e s t s were p e r f\u27 0 r m e d t o deter rn i n e the re 1 a t i 0 n s h i. p b e t w e e n t r a i n i n 9 a n d r ec i d i v i srn , t he re 1 -at j r. nship be twee n a•?e a nd completing t r a i n i n y \u3e and between age at release and recidivism- T h e m e d i a n a 9 e o f\u27 t h e p o p u 1 a t1 o n w a s 2 4.3 9 years- The younger subgroup ranged in age + row ly y e a. r s t0 2 4 y e a r s ■ The aide r s u. b 9 r o u. p rn e rn b e r s w ere greater than 25 years old. Treatment alone was not significant in reducing recidivism- Of all prisoners c o m pie t i n 9 v o c a t i o n a 1 t r a i n i n 9 6 3.3 \u27\u3c w ere o 1 d e r t h a n 2 5 y e a r s • ft 9 e w a s s i 9 n i f i c a n t i n c o m p 1 e t i n 9 t r e a t m e n t 1.1.1 i t h a chi s q V. a re sc o r e o ft 3 • 3 3 ? a t t h e • ft 5 1 e v e 1 o f s i 9n i ft i ca nce• Age a t t i rne oft re 1 ea se wa s r e 1. a t o d to reduced recidivism. This variable was significant w i t h a ch i sq u.ar e va ]. ue of 5 • 3 5 . a t the • ft 2 1 e• e 1 oft s i9 n ift icanc e. Prison e r s ove r 25 y ears of a g e had a recidivism rate of £2*4 \u27. while those prisoners who w ere y ou. n9e r h a d a r ec i d i v 1 s m r a t e o ft 4ft ■ 2. • The combined effect of treatment and age was significant i n r e duc 1 n9 r ec i d i v ism, w i t h a chi- s q u. ar e v a 1 u. e o ft a t the ■ d 5 1 e e 1 o ft s i 9 n i ft 1 c a n c e

Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells

The trans-activation response (TAR) RNA stem–loop that occurs at the 5′ end of HIV RNA transcripts is an important antiviral target and is the site of interaction of the HIV-1 Tat protein together with host cellular factors. Oligonucleotides and their analogues targeted to TAR are potential antiviral candidates. We have investigated a range of cell penetrating peptide (CPP) conjugates of a 16mer peptide nucleic acid (PNA) analogue targeted to the apical stem–loop of TAR and show that disulfide-linked PNA conjugates of two types of CPP (Transportan or a novel chimeric peptide R(6)-Penetratin) exhibit dose-dependent inhibition of Tat-dependent trans-activation in a HeLa cell assay when incubated for 24 h. Activity is reached within 6 h if the lysosomotropic reagent chloroquine is co-administered. Fluorescein-labelled stably-linked conjugates of Tat, Transportan or Transportan TP10 with PNA were inactive when delivered alone, but attained trans-activation inhibition in the presence of chloroquine. Confocal microscopy showed that such fluorescently labelled CPP–PNA conjugates were sequestered in endosomal or membrane-bound compartments of HeLa cells, which varied in appearance depending on the CPP type. Co-administration of chloroquine was seen in some cases to release fluorescence from such compartments into the nucleus, but with different patterns depending on the CPP. The results show that CPP–PNA conjugates of different types can inhibit Tat-dependent trans-activation in HeLa cells and have potential for development as antiviral agents. Endosomal or membrane release is a major factor limiting nuclear delivery and trans-activation inhibition

Synthesis and Splice-Redirecting Activity of Branched, Arginine-Rich Peptide Dendrimer Conjugates of Peptide Nucleic Acid Oligonucleotides

Arginine-rich cell-penetrating peptides have found excellent utility in cell and in vivo models for enhancement of delivery of attached charge-neutral PNA or PMO oligonucleotides. We report the synthesis of dendrimeric peptides containing 2- or 4-branched arms each having one or more R-Ahx-R motifs and their disulfide conjugation to a PNA705 splice-redirecting oligonucleotide. Conjugates were assayed in a HeLa pLuc705 cell assay for luciferase up-regulation and splicing redirection. Whereas 8-Arg branched peptide−PNA conjugates showed poor activity compared to a linear (R-Ahx-R)4−PNA conjugate, 2-branched and some 4-branched 12 and 16 Arg peptide−PNA conjugates showed activity similar to that of the corresponding linear peptide−PNA conjugates. Many of the 12- and 16-Arg conjugates retained significant activity in the presence of serum. Evidence showed that biological activity in HeLa pLuc705 cells of the PNA conjugates of branched and linear (R-Ahx-R) peptides is associated with an energy-dependent uptake pathway, predominantly clathrin-dependent, but also with some caveolae dependence

SELECTIVE MEASUREMENT OF α SMOOTH MUSCLE ACTIN: WHY β-ACTIN CAN NOT BE USED AS A HOUSEKEEPING GENE WHEN TISSUE FIBROSIS OCCURS

Abstract Background Prevalence of fibroproliferative diseases, including chronic kidney disease is rapidly increasing and has become a major public health problem worldwide. Fibroproliferative diseases are characterized by increased expression of α smooth muscle actin (α-SMA) that belongs to the family of the six conserved actin isoforms showing high degree homology. The aim of the present study was to develop real-time PCRs that clearly discriminate α-SMA and ß-actin from other actin isoforms. Results Real-time PCRs using self-designed mouse, human and rat specific α-SMA or ß-actin primer pairs resulted in the specific amplification of the artificial DNA templates corresponding to mouse, human or rat α-SMA or ß-actin, however ß-actin showed cross-reaction with the housekeeping γ-cyto-actin. We have shown that the use of improperly designed literary primer pairs significantly affects the results of PCRs measuring mRNA expression of α-SMA or ß-actin in the kidney of mice underwent UUO. Conclusion We developed a set of carefully designed primer pairs and PCR conditions to selectively determine the expression of mouse, human or rat α-SMA and ß-actin isoforms. We demonstrated the importance of primer specificity in experiments where the results are normalized to the expression of ß-actin especially when fibrosis and thus increased expression of α-SMA is occur

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Improved cell-penetrating peptide–PNA conjugates for splicing redirection in HeLa cells and exon skipping in mdx mouse muscle

Steric blocking peptide nucleic acid (PNA) oligonucleotides have been used increasingly for redirecting RNA splicing particularly in therapeutic applications such as Duchenne muscular dystrophy (DMD). Covalent attachment of a cell-penetrating peptide helps to improve cell delivery of PNA. We have used a HeLa pLuc705 cell splicing redirection assay to develop a series of PNA internalization peptides (Pip) conjugated to an 18-mer PNA705 model oligonucleotide with higher activity compared to a PNA705 conjugate with a leading cell-penetrating peptide being developed for therapeutic use, (R-Ahx-R)4. We show that Pip–PNA705 conjugates are internalized in HeLa cells by an energy-dependent mechanism and that the predominant pathway of cell uptake of biologically active conjugate seems to be via clathrin-dependent endocytosis. In a mouse model of DMD, serum-stabilized Pip2a or Pip2b peptides conjugated to a 20-mer PNA (PNADMD) targeting the exon 23 mutation in the dystrophin gene showed strong exon-skipping activity in differentiated mdx mouse myotubes in culture in the absence of an added transfection agent at concentrations where naked PNADMD was inactive. Injection of Pip2a-PNADMD or Pip2b-PNADMD into the tibealis anterior muscles of mdx mice resulted in ∼3-fold higher numbers of dystrophin-positive fibres compared to naked PNADMD or (R-Ahx-R)4-PNADMD

Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide

Sequence-specific interference with the nuclear pre-mRNA splicing machinery has received increased attention as an analytical tool and for development of therapeutics. It requires sequence-specific and high affinity binding of RNaseH-incompetent DNA mimics to pre-mRNA. Peptide nucleic acids (PNA) or phosphoramidate morpholino oligonucleotides (PMO) are particularly suited as steric block oligonucleotides in this respect. However, splicing correction by PNA or PMO conjugated to cell penetrating peptides (CPP), such as Tat or Penetratin, has required high concentrations (5–10 μM) of such conjugates, unless an endosomolytic agent was added to increase escape from endocytic vesicles. We have focused on the modification of existing CPPs to search for peptides able to deliver more efficiently splice correcting PNA or PMO to the nucleus in the absence of endosomolytic agents. We describe here R6-Penetratin (in which arginine-residues were added to the N-terminus of Penetratin) as the most active of all CPPs tested so far in a splicing correction assay in which masking of a cryptic splice site allows expression of a luciferase reporter gene. Efficient and sequence-specific correction occurs at 1 μM concentration of the R6Pen–PNA705 conjugate as monitored by luciferase luminescence and by RT-PCR. Some aspects of the R6Pen–PNA705 structure–function relationship have also been evaluated

Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO) and control peptide 3 (B-3-PMO and 3-B-PMO) were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO), further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO) was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG), indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.This is the publisher’s final pdf. The article is copyrighted by the American Society of Gene & Cell Therapy and published by the Nature Publishing Group. It can be found at: http://www.nature.com/mtna/index.html.Keywords: Antisense oligonucleotide, Exon skipping, Chimeric peptide conjugate, Duchenne muscular dystroph

Scientific Rationale of Saturn's In Situ Exploration

Remote sensing observations meet some limitations when used to study the bulk atmospheric composition of the giant planets of our solar system. A remarkable example of the superiority of in situ probe measurements is illustratedby the exploration of Jupiter, where key measurements such as the determination of the noble gases abundances and the precise measurement of the helium mixing ratio have only been made available through in situ measurements by the Galileo probe. This paper describes the main scienti-c goals to be addressed by the future in situ exploration of Saturn placing the Galileo probe exploration of Jupiter in a broader context and before the future probe exploration of the more remote ice giants. In situ exploration of Saturn's atmosphere addresses two broad themes that are discussedthroughout this paper : rst, the formation history of our solar system and second, the processes at play in planetary atmospheres. In this context, we detail the reasons why measurements of Saturn's bulk elemental and isotopiccomposition would place important constraints on the volatile reservoirs in the protosolar nebula. We also show that the in situ measurement of CO (or any other disequilibrium species that is depleted by reaction with water) in Saturn's upper troposphere may help constraining its bulk OH ratio. We compare predictions of Jupiter and Saturn's bulk compositions from different formation scenarios, and highlight the key measurements required to distinguish competing theories to shed light on giant planet formation as a common process in planetary systems with potential applications to mostextrasolar systems. In situ measurements of Saturn's stratospheric and tropospheric dynamics, chemistry and cloud-forming processes will provide access to phenomena unreachable to remote sensing studies. Dierent mission architectures are envisaged, which would benet from strong international collaborations, all based on an entry probe that would descend through Saturn's stratosphere and troposphere under parachute down to a minimum of 10 bars of atmospheric pressure. We rally discuss the science payload required on a Saturn probe to match the measurement requirements