We speculate that this derangement of LIGHT may be important for

We speculate that this derangement of LIGHT may be important for atherogenetic process of ischemic stroke.”
“Wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). To study the complex cascade associated with the continuous generation of particles, a robust animal model is essential. To date, an animal model that incorporates continuously delivered particles to an intramedullary orthopaedic implant has not been available. In this study, we

successfully infused clinically relevant ultra high molecular weight polyethylene particles, previously isolated from joint simulator tests, to the intramedullary space of the mouse femur for 4 weeks using a subcutaneous osmotic pump. Reduction of bone volume following

the 4-week infusion of UHMWPE was detected by microCT. UHMWPE Particles this website also changed the level of Alkaline Phosphatase expression in the infused femurs. Continuous infusion of particles to the murine bone-implant interface simulated the clinical scenario of local polymer wear particle generation and delivery in humans and can be used to further study the biological processes associated with GNS-1480 cost wear debris particles. (C) 2008 Elsevier Ltd. All rights reserved.”
“Brain edema is a major neurological complication of acute liver failure (ALF) and swelling of astrocytes (cytotoxic brain edema) is the most prominent neuropathological abnormality in this condition. Elevated brain ammonia level has been strongly implicated as an important factor in the mechanism of astrocyte swelling/brain edema in ALF. Recent studies, however, have suggested the possibility of a vasogenic component in the mechanism in ALF. We therefore examined the effect of ammonia KU-57788 on blood-brain barrier (BBB) integrity in an in vitro co-culture model of the BBB (consisting of primary cultures of rat brain endothelial cells and astrocytes). We found a minor degree of endothelial

permeability to dextran fluorescein (16.2%) when the co-culture BBB model was exposed to a pathophysiological concentration of ammonia (5 mM). By contrast, lipopolysaccharide (LPS), a molecule well-known to disrupt the BBB, resulted in an 87% increase in permeability. Since increased neurosteroid biosynthesis has been reported to occur in brain in ALF, and since neurosteroids are known to protect against BBB breakdown, we examined whether neurosteroids exerted any protective effect on the slight permeability of the BBB after exposure to ammonia. We found that a nanomolar concentration (10 nM) of the neurosteroids allopregnanolone (THP) and tetrahydrodeoxycorticosterone (THDOC) significantly reduced the ammonia-induced increase in BBB permeability (69.13 and 58.64%, respectively). On the other hand, we found a marked disruption of the BBB when the co-culture model was exposed to the hepatotoxin azoxymethane (218.

Thermogravimetric analysis (TGA) was used to study the thermal be

Thermogravimetric analysis (TGA) was used to study the thermal behavior of coatings. Physico-chemical and coating properties of the coatings were investigated by using standard methods. The results indicated that the bio-based wood finished PU coatings provided good mechanical weather resistance as well possessed

adequate coating properties for wood surface protections. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.”
“This study aimed to assess the exposure of free-living jaguars (Panthera onca) to Leptospira spp. and Brucella abortus in two Stattic conservation units in the Pantanal of Mato Grosso, Brazil. The presence of antibodies in blood samples of eleven jaguars was investigated using autochthonous antigens isolated in Brazil added to reference antigen collection applied to diagnosis of leptospirosis by Microscopic Agglutination Test (MAT). The Rose Bengal test was applied for B. abortus antibodies. Two (18.2%) jaguars were seroreactive for the Leptospira spp. antigen and the serovar considered as most infective in both animals was a Brazilian isolate of serovar Canicola (L01). All jaguars were

seronegative for B. abortus. These data indicate that the inclusion of autochthonous antigens in serological studies can significantly increase the number of reactive animals, as well as modify the epidemiological Prexasertib cell line profile of Leptospira spp. infection.”
“This study used 2DE to investigate how Arabidopsis thaliana modulates protein levels in response to freezing stress after sub-lethal exposure at HDAC phosphorylation -10 degrees C, both in cold-acclimated and in non-acclimated plants. A map was implemented in which 62 spots, corresponding to 44 proteins, were identified. Twenty-two spots were modulated upon treatments, and the corresponding proteins proved to be related to photosynthesis, energy metabolism, and stress response. Proteins demonstrated differences between control and acclimation conditions. Most of the acclimation-responsive proteins were either not further modulated or they

were down-modulated by freezing treatment, indicating that the levels reached during acclimation were sufficient to deal with freezing. Anabolic metabolism appeared to be down-regulated in favor of catabolic metabolism. Acclimated plants and plants submitted to freezing after acclimation showed greater reciprocal similarity in protein profiles than either showed when compared both to control plants and to plants frozen without acclimation. The response of non-acclimated plants was aimed at re-modulating photosynthetic apparatus activity, and at increasing the levels of proteins with antioxidant-, molecular chaperone-, or post-transcriptional regulative functions. These changes, even less effective than the acclimation strategy, might allow the injured plastids to minimize the production of non-useful metabolites and might counteract photosynthetic apparatus injuries. (C) 2012 Elsevier B.V. All rights reserved.

Outcome measures were AL, anastomotic bursting pressure, and deat

Outcome measures were AL, anastomotic bursting pressure, and death.\n\nResults: In the control group there was a 40% death rate with a 50% rate of AL. None of the sealants were able to diminish the rate of AL. Furthermore, use of the majority of sealants resulted in failure to thrive, increased rates of ileus, and higher mortality rates.\n\nConclusions: click here If sealing of a colorectal anastomosis could achieve a reduction of incidence of clinical AL, this would be a promising tool for prevention of leakage in colorectal surgery. In this study, we found no evidence that sealants

reduce leakage rates in a mouse model for AL. However, the negative results of this study make us emphasize the need of systemic research, investigating histologic tissue reaction of the bowel to different sealants, the capacity of sealants to form a watertight barrier, their time of degradation, and finally their results in large animal models for AL. (C) 2013 Elsevier Inc. All rights reserved.”
“After the clinical insertion of a bone biomaterial, the surrounding osteoblasts would migrate and attach to the implant surface and foster a microenvironment that largely determines the differentiation fate of the

comigrated mesenchymal stem cells. Whether the fostered microenvironment is suitable for osteogenic see more differentiation of mesenchymal stem cells is critical for the subsequent osseointegration. In this study, we determined (1) how the spherical or rod-shaped hydroxyapatite nanoparticles (nHA) incorporated poly(e-caprolactone) (PCL) films (PCL-spherical nHA, PCL-rod nHA) interact with primary human osteoblasts (HOBs); (2) how the microenvironment selleck rendered by their interaction affects osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs). HOBs were seeded on PCL, PCL-spherical nHA, and PCL-rod nHA films, respectively. When cultured alone, the HOBs on PCL-rod nHA

films showed most efficient osteoblastic differentiation compared with those on PCL or PCL-spherical nHA films. When cocultured with ASCs in an indirect coculture system, only the HOBs on PCL-rod nHA films up-regulated the gene expression of Runx2, bone sialoprotein, and osteocalcin of ASCs. Additionally, the HOBs on PCL-rod nHA films showed significant up-regulation of bone morphogenic protein 2 gene and protein expression and induced highest phosphorylated Smad1/5 protein level in ASCs. Treatment of the coculture medium with bone morphogenic protein 2 inhibitor (Noggin) largely abolished the osteogenic differentiation of the ASCs induced by the HOBs on PCL-rod nHA films. In conclusion, HOBs can not only best display their osteoblastic phenotype by culturing on PCL-rod nHA films but also render an optimal osteogenic niche for the differentiation of stem cells.

We found that, overall, hermaphrodites from populations with male

We found that, overall, hermaphrodites from populations with males tended to be more female than those from populations lacking males. Importantly, hermaphrodites’ investment in pollen

and PLX4032 clinical trial seed production was more plastic when they came from populations with males than without them, reducing their pollen production at low resource availability and increasing their seed production at high resource availability. These results are consistent with the hypothesis that plasticity in sex allocation is enhanced in hermaphrodites that have likely been exposed to variation in mating opportunities due to fluctuations in the frequency of co-occurring males.”
“A simple, rapid, and sensitive method based on liquid chromatography-tandem mass spectrometry for the quantitative determination of simvastatin in human plasma was developed and validated. After a simple extraction with methyl tert-butyl ether, the analyte and internal standard (lovastatin) were analyzed using reverse-phase

liquid chromatography, on a Kinetex C-18 column (100 x 4.6 mm, 2.6 Nutlin-3 order mu m) using acetonitrile: ammonium acetate (2 mM + 0.025 % formic acid) (70: 30, v/v) as a mobile phase in a run time of 3.5 min. Detection was carried out using electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode. The method was linear over 0.04-40.0 ng/mL concentration Buparlisib range. The mean extraction recovery of simvastatin was 82% (RSD within 15%). Intraday and interday precisions (as relative standard deviation) were all smaller than = 8,7% with accuracy (as relative error) of +/- 8%. This rapid and reliable method was successfully applied for a bioequivalence study of 40 mg of simvastatin orally disintegrating tablets in 44 healthy volunteers, showing that this method is suitable for the quantification of simvastatin in human plasma samples for pharmacokinetics and bioequivalence studies.”
“Context. – The cortico-basal syndrome (CBS), a complex clinical neurodegenerative disorder,

may have multiple aetiologies including corticobasal degeneration (CBD) and Alzheimer’s disease (AD). The aim of this study was to explore the brain perfusion profile in CBS patients according to the biological profile of CFS biomarkers (BM). Materials and methods. – Fifteen patients fulfilling clinical criteria of CBS underwent a brain perfusion scintigraphy with Tc-99m-ECD and a lumbar punction to determine the biochemical profile of CSF biomarkers (BM). Several groups were compared with SPM8 software: 1) 5 patients with SCB and with an AD CSF profile (CBS-AD); 2) 10 patients with CBS and not having an AD CSF profile (SCB-nonAD); 3) 24 healthy controls (Wit-N); 4) 24 typical amnestic (AD). Results.

Future use of these methods within a regulatory context requires,

Future use of these methods within a regulatory context requires, however, Geneticin order that they be optimized and standardized. Specifically, questions exist concerning gender differences in metabolism, cryopreservability of cells, and the accuracy of in vitro-in vivo scaling factors. 2. In this study, we evaluated hepatocytes from juvenile male and female trout. No gender differences in cell size, protein abundance, cytochrome P450 content, ethoxyresorufin-O-deethylase activity, uridine diphosphate glucuronosyltransferase activity or intrinsic clearance

of pyrene were observed for freshly isolated hepatocytes. There was a small difference in measured glutathione-S-transferase activity ( smaller than 25%; males bigger than females). 3. Cells were cryopreserved by two methods: direct placement into liquid N-2 vapor and controlled, slow-rate freezing. Comparable live recovery and enzymatic activity were observed regardless of freezing method or gender. Cells cryopreserved in liquid N-2 vapor exhibited activity levels similar to those of freshly isolated cells, although there were small this website but significant differences in pyrene clearance and glutathione-S-transferase activity (frozen smaller than fresh). Hepatocellularity values did not differ by sex. 4. These results suggest that hepatocytes from male and female juvenile trout may be used

interchangeably for in vitro-in vivo metabolism extrapolations.”
“The Main Glauconite Bed (MGB) is a pelleted greensand located at Stone City Bluff on the south bank of the Brazos PXD101 solubility dmso River in Burleson County, Texas. It was deposited during the Middle Eocene regional transgression on the Texas Gulf Coastal Plain. Stratigraphically it lies in the upper Stone City Member, Crockett Formation, Claiborne Group. Its mineralogy and geochemistry were examined in detail, and verdine facies minerals, predominantly odinite, were identified. Few glauconitic minerals were found in the green pelleted sediments of the MGB. Without detailed mineralogical work, glaucony facies minerals and verdine facies minerals are easily mistaken for one another. Their distinction has

value in assessing paleoenvironments. In this study, several analytical techniques were employed to assess the mineralogy. X-ray diffraction of oriented and un-oriented clay samples indicated a clay mixture dominated by 7 and 14 angstrom diffraction peaks. Unit cell calculations from XRD data for MGB pellets match the odinite-1M data base. Electron microprobe analyses (EMPA) from the average of 31 data points from clay pellets accompanied with Mossbauer analyses were used to calculate the structural formula which is that of odinite: Fe-0.89(3+) Mg-0.45 Al-0.67 Fe-0.30(2+) Ti-0.01 Mn-0.01) Sigma = 2.33 (Si-1.77 Al-0.23) O-5.00 (OH)(4.00). QEMSCAN (Quantitative Evaluation of Minerals by Scanning Electron Microscopy) data provided mineral maps of quantitative proportions of the constituent clays.


“Technological improvements have shifted the focus from da


“Technological improvements have shifted the focus from data generation to data analysis. The availability of huge amounts of data like transcriptomics, protemics and metabolomics raise new questions concerning suitable integrative analysis methods. We compare three integrative analysis techniques https://www.selleckchem.com/products/i-bet151-gsk1210151a.html (co-inertia analysis, generalized singular value decomposition and integrative biclustering) by applying them to gene and protein abundance data from six life cycle stages of Plasmodium falciparum. We create a network view of the GO terms associated to cell cycle stages by all three methods.”
“ObjectiveTo document staffing (medical, nursing, allied health [AH], administrative)

in Australian multidisciplinary persistent pain services and relate them to clinical activity levels. MethodsOf the 68 adult outpatient persistent pain services approached (Dec’08-Jan’10), 45 agreed to participate, received over 100 referrals/year, and met the contemporaneous International Association

for the Study of Pain criteria for Level 1 or 2 multidisciplinary services. Structured interviews with Clinical Directors collected quantitative data regarding staff resources (disciplines, amount), services provided, funding models, and activity levels. ResultsCompared with Level 2 clinics, Level 1 centers reported higher annual demand (referrals), clinical activity (patient numbers) and absolute Tubastatin A in vitro numbers of medical, nursing and administrative staff, but comparable numbers of AH staff. When staffing was assessed against activity levels, medical and nursing resources were consistent across services, but Level 1 clinics had relatively fewer AH and administrative staff. Metropolitan and rural services reported comparable

activity levels and discipline-specific staff ratios (except occupational therapy). The mean annual AH staffing for pain management group programs was 0.03 full-time equivalent staff per patient. ConclusionsReasonable consistency was demonstrated in the range and mix of most disciplines employed, suggesting they represented workable clinical structures. check details The greater number of medical and nursing staff within Level 1 clinics may indicate a lower multidisciplinary focus, but this needs further exploration. As the first multidisciplinary staffing data for persistent pain clinics, this provides critical information for designing and implementing clinical services. Mapping against clinical outcomes to demonstrate the impact of staffing patterns on safe and efficacious treatment delivery is required.”
“We have established strong linkage evidence that supports mapping autosomal-dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA is a rare neurological disorder whose phenotype encompasses both the central and the peripheral nervous system.

If susceptibility to RHD is delayed, myxomatosis will have a pron

If susceptibility to RHD is delayed, myxomatosis will have a pronounced effect on population extirpation when the two viruses coexist. This has important implications for wildlife management, because it is likely that such seasonal Akt inhibitor interplay and disease dynamics has a strong effect on long-term population viability for many species.”
“Cells of testicular tissues during fetal or neonatal periods have the ability to reconstruct the testicular architecture even after dissociation into single cells. This ability, however, has not been

demonstrated effectively in vitro. In the present study, we reconstructed seminiferous tubules in vitro that supported spermatogenesis to the meiotic phase. First, testicular cells of neonatal mice were dissociated enzymatically into single cells. Then, the cells formed aggregates in suspension culture and were transferred to the surface of agarose gel to continue the culture with a gas-liquid interphase method, and a tubular architecture gradually developed over the following 2 wk. Immunohistological examination confirmed Sertoli cells forming tubules and germ cells inside. With testicular tissues of Acr-GFP transgenic mice, the germ cells of which express GFP during meiosis, cell aggregates formed a tubular structure GSK2879552 and showed GFP expression in their reconstructed tissues. Meiotic figures were also confirmed

by regular histology and immunohistochemistry. In addition, we mixed cell lines of spermatogonial stem cells (GS cells) into the testicular cell suspension and found the incorporation of GS cells in the tubules of reconstructed tissues. When GS cells derived from Acr-GFP transgenic mice were used, GFP expression was observed, indicating that the spermatogenesis of GS cells was proceeding up to the meiotic phase. This in vitro reconstruction technique will be a useful method for the study of testicular organogenesis

and spermatogenesis.”
“To facilitate investigation of diverse rodent behaviours in rodents home cages, we have developed an integrated modular platform, the SmartCage (TM) system (AfaSci, Inc. Burlingame, CA, USA), mTOR inhibitor drugs which enables automated neurobehavioural phenotypic analysis and in vivo drug screening in a relatively higher-throughput and more objective manner. The individual platform consists of an infrared array, a vibration floor sensor and a variety of modular devices. One computer can simultaneously operate up to 16 platforms via USB cables. The SmartCage (TM) detects drug-induced increases and decreases in activity levels, as well as changes in movement patterns. Wake and sleep states of mice can be detected using the vibration floor sensor. The arousal state classification achieved up to 98% accuracy compared with results obtained by electroencephalography and electromyography.

These data indicate that MMF, through the depletion of guanosine,

These data indicate that MMF, through the depletion of guanosine, inhibits full cycle HCV JFH-1 replication in human hepatic cells. It is of interest to further determine whether MMF is indeed beneficial for HCV-infected transplant recipients in future clinical studies. (c) 2012 Elsevier B.V. All rights reserved.”
“Background: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic JQEZ5 mw suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic.\n\nMethods: We used a decision-analytic model, estimated

from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10%

S3I-201 inhibitor flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009-2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon.\n\nResults: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of

$472 M. In a pandemic similar to 2009-2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting find more in cost savings of $1.0 B compared to PCV7.\n\nConclusions: In a flu pandemic similar to the 2009-2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs.”
“Borderline Personality Disorder (BPD) constitutes a profound instability with dysfunction in three psychopathological dimensions as cognitive-perceptual symptoms, affective dysregulation and behavioral impulsivity. Psychopharmacotherapy has a crucial role in the treatment of this complex disorder and targets the respective core symptoms. It comprises basically atypical anti-psychotics, antidepressant agents and moodstabilizers, often requiring a combination of these substances in case of complex, multidimensional symptoms.

(C) 2008 Elsevier B V All rights reserved “
“The tumor necr

(C) 2008 Elsevier B.V. All rights reserved.”
“The tumor necrosis factor superfamily (TNFSF) consists of more than 20 members that can modulate cellular and immunological functions, including cell survival and the stimulation of an inflammatory response. Ro-3306 supplier Many TNF superfamily members display potent anticancer activity when used as recombinant proteins in vitro and in vivo. While TNF, TRAIL and FasL have already been used as payloads in antibodybased

pharmacodelivery strategies, most TNF superfamily members have not yet been investigated as antibody payloads. Here, we report the cloning, production and characterization of eight novel antibody fusion proteins based on CD4OL, FasL, TRAIL, LiGHT, VEGI, lymphotoxin alpha, lymphotoxin beta and lymphotoxin alphal /beta2. The monoclonal antibody F8 was chosen as fusion partner of proven tumor targeting performance, which recognizes the alternatively-spliced EDA domain of fibronectin, a marker of angiogenesis. A quantitative biodistribution analysis performed with radioiodinated protein preparations in tumor-bearing mice revealed that TRAIL and lymphotoxin

alphal /beta2 were able to selectively accumulate at the tumor site, while all other members of the TNF superfamily abrogated p38 MAPK cancer the selective tumor targeting performance of the parental antibody or accumulated also in healthy tissues. The study indicates that even cytokines, which are closely related in terms of structure and function, may have a substantially different impact on the biodistribution and functional p38 MAPK signaling pathway properties of the corresponding fusions with disease-homing antibodies. (C) 2013 Elsevier B.V. All rights reserved.”
“Background: Our study objective was to describe the frequency, indications, and outcomes after inferior vena cava (IVC) filter placement in a population-based sample of residents of the Worcester, Massachusetts, metropolitan area who had been diagnosed as having acute venous thromboembolism

(VTE) in 1999, 2001, and 2003.\n\nMethods: A retrospective chart review of inpatient and outpatient medical records was conducted. Recorded indication(s) for IVC filter placement was determined among a subset of cases from 3 Worcester tertiary care hospitals. Three thrombosis specialists assessed the appropriateness of IVC filter placement.\n\nResults: Of 1547 greater Worcester residents with validated acute VTE and without a prior IVC filter, 203 (13.1%) had an IVC filter placed after acute VTE. Patients with an IVC filter were older, had more comorbidities, and had a higher mortality rate during 3 years of follow-up. There was unanimous agreement by panel members that the use of an IVC filter was appropriate in 51% of cases and inappropriate in 26% of cases, with no consensus in the remaining 23%.\n\nConclusions: In this community-based study, IVC filters were frequently used in the treatment of patients with acute VIE.

Mean follow-up

Mean follow-up Selleckchem Alisertib time of all seven patients was 19.5 (range, 2-60) months. No patient developed recurrence of exposure during follow-up. All patients were fitted with an acceptable prosthesis and had satisfactory cosmetic and functional results.\n\nConclusions: The most common complication of orbital implant is exposure, caused by breakdown of the covering layers, leading to extrusion. Several methods were reported to manage the exposed implants. We report our experience of treating implant exposure with extraocular muscle flaps to establish a well-vascularized environment that supplies both the wrapping material and the overlying

ocular surface tissue. We believe it can work as a good strategy to manage or to prevent orbital implant exposure.”
“While the ecological impacts of invasive species have EVP4593 chemical structure been demonstrated for many taxonomic groups, the potential effects of behavioural variation among non-native individuals (i.e. personality) on these impacts have been largely overlooked. This is

despite the fact that recent studies have demonstrated that, by nature, the three first stages of biological invasions (i.e. transport, establishment and spread) can lead to personality-biased populations. Freshwater ecosystems provide a unique opportunity to investigate this issue, notably because the ecological impacts of non-native species have been extensively documented and because animal personality has been widely studied using freshwater model species. Here, we aim at developing some perspectives on the potential effects of animal personality check details on the ecological impacts of freshwater non-native species across levels of biological organizations. At the individual level, personality types have been demonstrated to affect the physiology, metabolism, life history traits and fitness of individuals. We used these effects to discuss how they could subsequently impact invaded populations and, in turn, recipient

communities. We also discussed how these might translate into changes in the structure of food webs and the functioning of invaded ecosystems. Finally we discussed how these perspectives could interact with the management of invasive species.”
“Inactivation of the retinoblastoma (Rb) tumor suppressor protein is widespread in human cancers. Inactivation of Rb is thought to be initiated by association with Raf-1 (C-Raf) kinase, and here we determined how RRD-251, a disruptor of the Rb-Raf-1 interaction, affects pancreatic tumor progression. Assessment of phospho-Rb levels in resected human pancreatic tumor specimens by immunohistochemistry (n – 95) showed that increased Rb phosphorylation correlated with increasing grade of resected human pancreatic adenocarcinomas (P = 0.0272), which correlated with reduced overall patient survival (P = 0.0186).