Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia

The molecular basis of schizophrenia is poorly understood; however, different brain regions are believed to play distinct roles in disease symptomology. We have studied gene expression in the superior temporal cortex (Brodmann area 22; BA22), which may play a role in positive pathophysiology, and compared our results with data from the anterior prefrontal cortex (BA10), which shows evidence for a role in negative symptoms. Genome‐wide mRNA expression was determined in the BA22 region in 23 schizophrenics and 19 controls and compared with a BA10 data set from the same subjects. After adjustments for confounding sources of variation, we carried out GeneGO pathway enrichment analysis in each region. Significant differences were seen in age‐related transcriptional changes between the BA22 and the BA10 regions, 21.8% and 41.4% of disease‐associated transcripts showing age association, respectively. After removing age associated changes from our data, we saw the highest enrichment in processes mediating cell adhesion, synaptic contact, cytoskeletal remodelling, and apoptosis in the BA22 region. For the BA10 region, we observed the strongest changes in reproductive signalling, tissue remodelling, and cell differentiation. Further exploratory analysis also identified potentially disease‐relevant processes that were undetected in our more stringent primary analysis, including autophagy in the BA22 region and the amyloid process in the BA10 region. Collectively, our analysis suggests disruption of many common pathways and processes underpinning synaptic plasticity in both regions in schizophrenia, whereas individual regions emphasize changes in certain pathways that may help to highlight pathway‐specific therapeutic opportunities to treat negative or positive symptoms of the disease. © 2011 Wiley‐Liss, Inc.
Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder: a systematic chart review of 62 cases.

OBJECTIVE Children and adolescents with attention-deficit hyperactivity disorder (ADHD), with or without psychostimulant treatment, frequently suffer from sleep disturbances. This report evaluates the use of clonidine in the treatment of sleep disturbances associated with ADHD. METHOD A systematic search of a computerized database in an outpatient pediatric psychopharmacology unit of patients treated with clonidine for ADHD-associated sleep disturbances (N = 62; 42 children and 20 adolescents) was performed. Patients were rated retrospectively about the type and severity of sleep disturbances at baseline and after treatment with clonidine. RESULTS A majority of patients (85%) treated with clonidine for ADHD-associated sleep disturbances were considered to be much to very much improved by the National Institute of Mental Health global assessment of improvement (sleep). Nighttime clonidine doses ranged from 50 to 800 micrograms (mean +/- SEM; 157 +/- 14 micrograms), and subjects received clonidine for 35.5 +/- 3.5 months. There was no association between response and age group, gender, comorbidity, or concurrent pharmacotherapy. Children and adolescents with ADHD with baseline, medicine-induced, or medicine-exacerbated sleep disturbances responded equally well to clonidine treatment. Mild adverse effects were reported in 19 subjects (31%). CONCLUSIONS These findings suggest that clonidine may be an effective agent for sleep disturbances associated with ADHD, or its treatment, and warrant further controlled investigations.
LABORATORY AND THEORETICAL RESULTS FROM INVESTIGATIONS OF CO 2 SOLUBILITY IN GEOTHERMAL RESERVOIRS

This paper considers the idea of CO2 injection into deep thermal reservoirs. The application of this research is either to the goal of carbon sequestration or the use of CO2 as the working fluid in an Engineered Geothermal Systems (EGS). Sequestration may occur in a number of ways such as via: solubility trapping, mineralization, impermeable caprocks, or capillary forces. This research presents evidence for a new phenomenon named ―active phase change‖ (APC), which refers to the combined effect of CO2 solubility with standard hydrodynamics on the multiphase flow of CO2 and water through porous media. Laboratory experiments and theoretical work were designed to investigate thermodynamic effects that may occur when solubility is taken into account. A core-scale experiment measured relative permeabilities in the two-phase system, a micromodel experiment qualitatively observed the dynamic dissolution phenomenon, and theoretical analyses put the findings in context and provided a framework to predict results under varied conditions. The purpose of this research was to analyze and quantify the magnitude of dissolution effects through laboratory and theoretical work. An additional goal was to evaluate the time and length-scales of dissolution and diffusion effects relative to standard hydrodynamic behavior. This paper concludes with recommendations for improvements to the experimental set-up and for future work.
Atp10p Assists Assembly of Atp6p into the F0 Unit of the Yeast Mitochondrial ATPase*

The F0F1-ATPase complex of yeast mitochondria contains three mitochondrial and at least 17 nuclear gene products. The coordinate assembly of mitochondrial and cytosolic translation products relies on chaperones and specific factors that stabilize the pools of some unassembled subunits. Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F0 sector of the ATPase. Here we show that, following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p. This interaction is required for the integration of Atp6p into a partially assembled subcomplex of the ATPase. Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type. Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits.
Correlation Between First- and Early Third- Trimester Glucose Screening Test Results

One hundred twenty-four normal gravidas had paired first and early third-trimester (26-32 weeks) 1-hour oral glucose screening tests performed. First-trimester oral glucose screening test values correlated significantly with third trimester glucose screening test results for the entire population, for whites and non-whites, and for normal-weight and obese patients. First-trimester oral glucose screening test values at or below 110 mg/dL were seldom associated with third-trimester oral glucose screening test results at or above 135 mg/dL and were not associated with abnormal 3-hour glucose tolerance test (GTT) results. Nine of the gravidas (7.3%) were diagnosed with gestational diabetes mellitus during the third trimester, all of whom had first-trimester glucose screening test results above 110 mg/dL. The difference in incidence of gestational diabetes mellitus between gravidas having first-trimester glucose screening test results at or below 110 mg/dL (0%) and those having values above 110 mg/dL (16.4%) was highly significant (P<.0001). For patients with first-trimester glucose screening test values at or below 110 mg/dL, third-trimester glucose screening may be unnecessary. In contrast, for gravidas having first-trimester glucose screening test results at or above 135 mg/dL, there is a high positive predictive value for elevated repeat glucose screening test results during the early third trimester. Patients having elevated first-trimester glucose screening values at or above 140 mg/dL are at particularly high risk for elevated glucose screening test results later in pregnancy and should forego repeat 1-hour third-trimester glucose screening in favor of a direct third-trimester 3-hour GTT.
Does T'ai Chi Gait Reduce External Knee Adduction Moment?

INTRODUCTION T'ai chi chuan is a beneficial exercise of improving health and function. Biomechanical insights of t'ai chi chuan are less understood. OBJECTIVES To study t'ai chi gait (TCG), a common form of t'ai chi chuan in order to quantify external knee adduction moment (EKAM) as a key indicator of mechanical loading of the medial compartment of the knee compared with normal walking (NW). DESIGN A quantitative biomechanics approach to determine peak EKAM for NW and TCG. RESULTS There were a tri-modal pattern of EKAM during TCG and a bimodal pattern of EKAM during normal walking. In addition, subsequent analysis showed a 25%-47% reduction in peak EKAM during double support phases of TCG compared with NW; the peak EKAM of TCG during single-limb support phase showed significantly higher magnitude than the other two double-support phases. CONCLUSION These results indicate that t'ai chi chuan might be a beneficial intervention for reducing the medial mechanical load at the knee joint, particularly during the first double-support phases of TCG, but the special consideration of higher peak EKAM of single-limb support phase is needed during regular t'ai chi chuan practice.
5 Users Every Friday: A Case Study in Applied Research

In 2007 a large consumer electronics retailer faced significant business challenges. In pursuit of new modes of strategic flexibility and fast execution, the e-commerce division transformed its culture around Agile principles and the user experience team adapted its practices to the new paradigm. How would increased velocity affect the quality of the functionality produced? How would time-intensive activities like usability research be affected? This paper presents a case study describing successes and failures while integrating continuous research into Agile projects.
Tumor Cell Lysis by Complement Antigen G250 Enhances C3 Deposition and Regulator CD55 and the Renal Tumor-Associated Against Both the Membrane-Bound Complement A Bispecific Monoclonal Antibody Directed

Tumor cells may inhibit the induction of a complement-mediated inﬂammatory response through overexpression of membrane-bound regulators of complement activation. Therefore, it is of interest to determine the most efﬁcient approach to block these membrane-bound complement regulators on tumor cells. In the present study, we ﬁrst generated a bispeciﬁc mAb directed against both CD55, using the functional blocking mAb MBC1, and the highly expressed HLA class I molecule as a model for a tumor-associated Ag, using the mAb W6/32. Tumor cells opsonized with bispeciﬁc mAb W6/32*MBC1, then exposed to complement and subsequently stained for C3 deposition, were assessed by ﬂow cytometric analysis. We found that opsonization with W6/32*MBC1 resulted in a 92% enhancement of C3 deposition on renal tumor cells as compared with opsonization with W6/32 alone and a 17% enhancement of the C3 deposition as compared with incubation with a mixture of both parental mAb. Based on these results, we developed a bispeciﬁc mAb recognizing both CD55 and the relatively low expressed renal tumor-associated Ag G250. Increasing concentrations of the bispeciﬁc mAb G250*MBC1 resulted in a 25 to 400% increase in C3 deposition on renal tumor cells as compared with C3 deposition in the presence of the parental mAb G250 alone. G250*MBC1 enhanced C3 deposition by 21% in comparison with a mixture of both parentals. Furthermore, opsonization of tumor cells with G250*MBC1 rendered these cells more sensitive to complement-mediated lysis. In conclusion, the bispeciﬁc mAb G250*MBC1 induces deposition of C3 and tumor cell lysis more efﬁciently than G250 alone. The Journal Based on this assumption, bispeciﬁc mAb were produced with one arm directed against a tumor-associated Ag and the other arm against the mRCA, CD55. This complement regulatory protein is involved in the irreversible dissociation of C3/C5 convertases (15). Blocking the function of CD55 results in membrane deposition of C3b and generation of chemotactic factors such as C5a. In this study, the applicability of a bispeciﬁc mAb for future immunotherapy was evaluated. We ﬁrst generated a bispeciﬁc mAb simultaneously directed against CD55 and the highly expressed HLA class I molecule as a model for a tumor-associated Ag. Based on the positive results obtained, a bispeciﬁc mAb directed against both CD55 and the renal tumor-associated Ag G250, which is expressed at a lower density than HLA class I, was generated.
Iobitridol, A New Nonionic Low‐Osmolality Contrast Agent, and Iohexol: Impact on Renal Histology in the Rat

RATIONALE AND OBJECTIVESTo compare the histologic effects on rat tubular cells of two nonionic contrast media with equivalent osmolalities and viscosities. METHODSHistologic, functional (creatinine clearance), and biochemical (proteinuria and enzymuria) profiles of iohexol and iobitridol (both at 350 mg 1/mL) were compared in the uninephrectomized rat. A control group (n = 14) received compared isotonic saline solution. Test substances (3 mL) were injected into the kidney at a rate of 1 mL/minute while transitory ischemia was induced by clamping the aorta above the renal artery. RESULTSIn terms of their (moderate) effects on creatinine clearance, proteinuria, and urinary N-acetyl-beta–D-glucosaminidase activity, no statistically significant difference was detected between the two low-osmolar contrast agents either 24 or 48 hours after injection. However, blinded histologic analysis of the kidneys showed significantly greater epithelial cell vacuolization in the proximal convoluted tubules of the outer cortex with iohexol (14 of 14 rats versus 3 of 14 rats for iobitridol; P < .001). The same degree of vacuolization in the inner cortex was observed for all three substances. Iobitridol also induced fewer congestive lesions in the glomerular capillaries than iohexol (4 of 14 versus 10 of 14, respectively; P < .05) and saline (5 of 6; P < .05). It is difficult to explain the lesser degree of cytoplasmic vacuolization using standard physiochemical parameters. CONCLUSIONAlthough iobitridol and iohexol showed similar functional and biochemical profiles when selectively injected into the single remaining kidney of rats, iobitridol induced significantly less tubular vacuolization and capillary congestion than iohexol.
Targeting of the Orphan Receptor GPR35 by Pamoic Acid: A Potent Activator of Extracellular Signal-Regulated Kinase and β-Arrestin2 with Antinociceptive Activity

Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that pamoic acid is a potent GPR35 agonist. Pamoic acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that pamoic acid induces a Gi/o-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent.
Full order dynamic output feedback ℋ∞ control for continuous-time switched linear systems

This paper is devoted to the analysis and solution of the output feedback H∞ control design problem for continuous-time switched linear systems. More specifically, the main goal is to design a switching rule together with a full order dynamic linear controller to satisfy a pre-specified H∞ level defined by the L2 gains from the input to the output signal. The results reported in this paper are based on the so called Lyapunov-Metzler inequalities which express a sufficient condition for switched linear systems global stability. The solution of the previously mentioned output feedback control design problem through an LMI-based method is the main contribution of the present paper. An academic example borrowed from the literature is used for illustration.
Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells

Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, and efficacy of adoptively transferred CD8+ T cell clones targeting the tumor-associated antigens, MART1/MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 × 106 units/m2 twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1/MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persist in vivo in response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.
A randomized phase II study of aromatase inhibitors plus metformin in pre-treated postmenopausal patients with hormone receptor positive metastatic breast cancer

Background Everolimus significantly improves progression-free survival (PFS) and has been approved to use in aromatase inhibitor pretreated patients with hormone receptor positive advanced breast cancer. Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors. Methods 60 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer were randomly assigned 1:1 to aromatase inhibitor (exemestane 25mg/d or letrozole 2.5mg/d depending on the most recent treatment) plus metformin (0.5g bid, orally) or placebo. The primary endpoint was PFS, and secondary endpoints were objective response rate, clinical benefit rate, overall survival and safety. Results Median PFS was 4.7 months in the combination group and 6.0 months in the control group (hazard ratio, 1.2; 95% confidence interval [CI], 0.7 to 2.1; P =0.48). ORR was 6.7% in the combination group and 0% in the control group (odds ratio for ORR not available; P =0.99), and CBR was 33.3% and 50.0%, respectively (OR for CBR 0.5; 95% CI, 0.2 to 1.4; P=0.15). No significant difference in overall survival was observed between the combination and control groups (median OS, 30.9 vs. 32.4 months; P = 0.81). Subgroup analyses didn't find any specific population favoring the combination treatment. No substantial difference in incidence or severity of adverse events was seen between the two treatment groups. Conclusion This randomized phase II clinical trial failed to show an improved efficacy with the addition of metformin to endocrine therapy, although with excellent tolerability.
Risk of Cancer in Autoimmune Pancreatitis: A Case-Control Study and Review of the Literature

Objectives The risk of pancreatic and extrapancreatic cancer in autoimmune pancreatitis (AIP) has not been systematically evaluated. We compared the risk of malignancy in AIP patients and matched control subjects. Methods We identified 116 subjects with AIP from a prospectively maintained database. From patients evaluated in primary care clinics, we selected 3 control subjects for each AIP patient matched on age, registration date, and sex (n = 344) . Risk for developing cancer after the index date was compared using a stratified Cox model. Results The proportion of patients diagnosed with cancer before AIP diagnosis (10.3%) was lower than that in the matched control subjects (17.4%). After a median follow-up of over 3 years, the risk of developing cancer after the index date was similar in AIP and control subjects (hazard ratio, 0.64; 95% confidence interval, 0.27–1.51). The 3 most commonly diagnosed malignancies in the AIP group were prostate cancer, lymphoma, and bladder cancer. Conclusions Cancer risk before and after diagnosis of AIP is similar to that of control subjects. Specifically, there is no increased risk of cancer immediately preceding or following AIP diagnosis. Additional follow-up is needed to determine if there is a cumulative increase in cancer risk in AIP.
Mechanism for the enhancement effect of fatty acids on the percutaneous absorption of propranolol.

The effects of a series of fatty acids on the percutaneous absorption of propranolol (PL) through rabbit skin and the mechanism by which fatty acids facilitate the skin penetration of PL were examined in vitro and in vivo using a gel base. Lauric and myristic acids, at the fatty acid:PL molar ratio of 1:1 were the most potent agents in increasing the skin penetration, giving the largest penetration rate (Js) and penetration coefficient (Kp) of PL. The molar ratio of 2:1 also exerted a large enhancing effect, comparable to that with a molar ratio of 1:1. When the enhancing effects of lauric acid, its amide, and its methyl ester were compared, the free acid gave the highest Js and Kp values. The plasma PL concentrations were significantly higher and more sustained after a single percutaneous application of the formulation with lauric acid than those after the formulation without the acid. The mechanism for the enhancing effect was examined by measuring IR and 13C NMR spectra, the solubility in buffer, and the apparent partition coefficient of PL. Additionally, the penetration of PL and lauric acid, as co-penetrants, through rabbit skin and shed snake skin were evaluated. The IR spectra of the mixture of PL with lauric acid (molar ratio, 1:1) was characterized by an extreme shift of the CO peak. Comparison of the NMR spectra of PL, lauric acid, and the mixture suggested that the carbonyl group of lauric acid interacted with the amino and hydroxyl groups of PL, probably by charge interaction. (ABSTRACT TRUNCATED AT 250 WORDS)
A possible role for CD8+ and non‐CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema

CD8+ cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8+ T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B‐positive cells in relation to CD8+ cells in the small airway walls of emphysema.