5,617 research outputs found
Case Management: Using Harm Reduction with Chemically Addicted Clients
The research surrounding the outcomes of harm reduction is gaining momentum, and the awareness of the harm reduction philosophy is becoming more widespread among social workers. Providers who utilize harm reduction are often the people that work directly with the most disenfranchised people in our nation. These providers most often deal with clients who are chemically addicted. Current research indicates that harm reduction can be beneficial for the clients who use chemicals. This research project sought to collect information about the experiences of case managers who implement harm reduction. The case managers expressed that the utilization of harm reduction could be difficult at times because there is a need for more provider trainings on the model; and harm reduction could be hard to implement when working with professionals from cross-disciplinary fields and chemical health professionals from the abstinence-based community. However, case managers felt that implementing harm reduction supported their ability to create a meaningful relationship with their clients, and it also lowered their general stress level. The results of this research will be used to inform social service providers about the struggles and successes that some case managers who implement harm reduction experience when working with chemically addicted clients
Case Management: Using Harm Reduction with Chemically Addicted Clients
The research surrounding the outcomes of harm reduction is gaining momentum, and the awareness of the harm reduction philosophy is becoming more widespread among social workers. Providers who utilize harm reduction are often the people that work directly with the most disenfranchised people in our nation. These providers most often deal with clients who are chemically addicted. Current research indicates that harm reduction can be beneficial for the clients who use chemicals. This research project sought to collect information about the experiences of case managers who implement harm reduction. The case managers expressed that the utilization of harm reduction could be difficult at times because there is a need for more provider trainings on the model; and harm reduction could be hard to implement when working with professionals from cross-disciplinary fields and chemical health professionals from the abstinence-based community. However, case managers felt that implementing harm reduction supported their ability to create a meaningful relationship with their clients, and it also lowered their general stress level. The results of this research will be used to inform social service providers about the struggles and successes that some case managers who implement harm reduction experience when working with chemically addicted clients
Task 11 - systems analysis of environmental management technologies
A review was conducted of three systems analysis (SA) studies performed by Lockheed Idaho Technologies Company (LITCO) on integrated thermal treatment systems (ITTs) and integrated nonthermal treatment systems (INTSs) for the remediation of mixed low-level waste (MLLW) stored throughout the U.S. Department of Energy (DOE) weapons complex. The review was performed by an independent team led by the Energy & Environment Research Center (EERC), including Science Applications International Corporation (SAIC), the Waste Policy Institute (WPI), and Virginia Tech
PP2A Regulates Phosphorylation-Dependent Isomerization of Cytoplasmic and Mitochondrial-Associated ATR by Pin1 in DNA Damage Responses
Ataxia telangiectasia and Rad3-related protein (ATR) is a serine/threonine-protein kinase of the PI3K family and is well known for its key role in regulating DNA damage responses in the nucleus. In addition to its nuclear functions, ATR also was found to be a substrate of the prolyl isomerase Pin1 in the cytoplasm where Pin1 isomerizes cis ATR at the Ser428-Pro429 motif, leading to formation of trans ATR. Cis ATR is an antiapoptotic protein at mitochondria upon UV damage. Here we report that Pin1’s activity on cis ATR requires the phosphorylation of the S428 residue of ATR and describe the molecular mechanism by which Pin1-mediated ATR isomerization in the cytoplasm is regulated. We identified protein phosphatase 2A (PP2A) as the phosphatase that dephosphorylates Ser428 following DNA damage. The dephosphorylation led to an increased level of the antiapoptotic cis ATR (ATR-H) in the cytoplasm and, thus, its accumulation at mitochondria via binding with tBid. Inhibition or depletion of PP2A promoted the isomerization by Pin1, resulting in a reduction of cis ATR with an increased level of trans ATR. We conclude that PP2A plays an important role in regulating ATR’s anti-apoptotic activity at mitochondria in response to DNA damage. Our results also imply a potential strategy in enhancing cancer therapies via selective moderation of cis ATR levels
Checkpoint Kinase ATR Promotes Nucleotide Excision Repair of UV-Induced DNA Damage via Physical Interaction Withxeroderma Pigmentosum Group A
In response to DNA damage, eukaryotic cells activate a series of DNA damage-dependent pathways that serve to arrest cell cycle progression and remove DNA damage. Coordination of cell cycle arrest and damage repair is critical for maintenance of genomic stability. However, this process is still poorly understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint are the major pathways responsible for repair of UV-induced DNA damage. Here we show that ATR physically interacts with the NER factor Xeroderma pigmentosum group A (XPA). Using a mass spectrometry-based protein footprinting method, we found that ATR interacts with a helixturn-helix motif in the minimal DNA-binding domain of XPA where anATRphosphorylation site (serine 196) is located.XPAdeficient cells complemented with XPA containing a point mutation of S196A displayed a reduced repair efficiency of cyclobutane pyrimidine dimers as compared with cells complemented with wild-type XPA, although no effect was observed for repair of (6-4) photoproducts. This suggests that the ATR-dependent phosphorylation of XPA may promote NER repair of persistentDNAdamage. In addition, a K188A point mutation of XPA that disrupts the ATR-XPA interaction inhibits the nuclear import of XPA after UV irradiation and, thus, significantly reduced DNA repair efficiency. By contrast, the S196A mutation has no effect on XPA nuclear translocation. Taken together, our results suggest that the ATR-XPA interaction mediated by the helix-turn-helix motif of XPA plays an important role in DNA-damage responses to promote cell survival and genomic stability after UV irradiation
ATR Prevents Ca\u3csup\u3e2+\u3c/sup\u3e Overload-Induced Necrotic Cell Death Through Phosphorylation-Mediated Inactivation of PARP1 Without DNA Damage Signaling
Hyperactivation of PARP1 is known to be a major cause of necrotic cell death by depleting NAD+/ATP pools during Ca2+ overload which is associated with many ischemic diseases. However, little is known about how PARP1 hyperactivity is regulated during calcium overload. In this study we show that ATR kinase, well known for its role in DNA damage responses, suppresses ionomycin, glutamate, or quinolinic acid-induced necrotic death of cells including SH-SY5Y neuronal cells. We found that the inhibition of necrosis requires the kinase activity of ATR. Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments. This site-specific phosphorylation inactivates PARP1, inhibiting ionophore-induced necrosis. Strikingly, all of this occurs in the absence of detectable DNA damage and signaling up to 8 hours after ionophore treatment. Furthermore, little AIF was released from mitochondria/cytoplasm for nuclear import, supporting the necrotic type of cell death in the early period of the treatments. Our results reveal a novel ATR-mediated anti-necrotic mechanism in the cellular stress response to calcium influx without DNA damage signaling
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
Search for anomalous t t-bar production in the highly-boosted all-hadronic final state
A search is presented for a massive particle, generically referred to as a
Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are
sufficiently massive to produce highly Lorentz-boosted top quarks, which yield
collimated decay products that are partially or fully merged into single jets.
The analysis uses new methods to analyze jet substructure, providing
suppression of the non-top multijet backgrounds. The analysis is based on a
data sample of proton-proton collisions at a center-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits
in the range of 1 pb are set on the product of the production cross section and
branching fraction for a topcolor Z' modeled for several widths, as well as for
a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any
enhancement in t t-bar production beyond expectations of the standard model for
t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version
includes a minor typo correction that will be submitted as an erratu
Combined search for the quarks of a sequential fourth generation
Results are presented from a search for a fourth generation of quarks
produced singly or in pairs in a data set corresponding to an integrated
luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in
2011. A novel strategy has been developed for a combined search for quarks of
the up and down type in decay channels with at least one isolated muon or
electron. Limits on the mass of the fourth-generation quarks and the relevant
Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a
simple extension of the standard model with a sequential fourth generation of
fermions. The existence of mass-degenerate fourth-generation quarks with masses
below 685 GeV is excluded at 95% confidence level for minimal off-diagonal
mixing between the third- and the fourth-generation quarks. With a mass
difference of 25 GeV between the quark masses, the obtained limit on the masses
of the fourth-generation quarks shifts by about +/- 20 GeV. These results
significantly reduce the allowed parameter space for a fourth generation of
fermions.Comment: Replaced with published version. Added journal reference and DO
Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV
The t t-bar production cross section (sigma[t t-bar]) is measured in
proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS
experiment, corresponding to an integrated luminosity of 2.3 inverse
femtobarns. The measurement is performed in events with two leptons (electrons
or muons) in the final state, at least two jets identified as jets originating
from b quarks, and the presence of an imbalance in transverse momentum. The
measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/-
2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction
of the standard model.Comment: Replaced with published version. Included journal reference and DO
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