Miracle-dz/UniFAR-FTUs huggingface dataset:
Maintenance of muscle mass and load-induced growth in Muscle RING Finger 1 null mice with age

Age‐related loss of muscle mass occurs to varying degrees in all individuals and has a detrimental effect on morbidity and mortality. Muscle RING Finger 1 (MuRF1), a muscle‐specific E3 ubiquitin ligase, is believed to mediate muscle atrophy through the ubiquitin proteasome system (UPS). Deletion of MuRF1 (KO) in mice attenuates the loss of muscle mass following denervation, disuse, and glucocorticoid treatment; however, its role in age‐related muscle loss is unknown. In this study, skeletal muscle from male wild‐type (WT) and MuRF1 KO mice was studied up to the age of 24 months. Muscle mass and fiber cross‐sectional area decreased significantly with age in WT, but not in KO mice. In aged WT muscle, significant decreases in proteasome activities, especially 20S and 26S β5 (20–40% decrease), were measured and were associated with significant increases in the maladaptive endoplasmic reticulum (ER) stress marker, CHOP. Conversely, in aged MuRF1 KO mice, 20S or 26S β5 proteasome activity was maintained or decreased to a lesser extent than in WT mice, and no increase in CHOP expression was measured. Examination of the growth response of older (18 months) mice to functional overload revealed that old WT mice had significantly less growth relative to young mice (1.37‐ vs. 1.83‐fold), whereas old MuRF1 KO mice had a normal growth response (1.74‐ vs. 1.90‐fold). These data collectively suggest that with age, MuRF1 plays an important role in the control of skeletal muscle mass and growth capacity through the regulation of cellular stress.
Forward sensitivity analysis for contracting stochastic systems

Abstract In this paper we investigate gradient estimation for a class of contracting stochastic systems on a continuous state space. We find conditions on the one-step transitions, namely differentiability and contraction in a Wasserstein distance, that guarantee differentiability of stationary costs. Then we show how to estimate the derivatives, deriving an estimator that can be seen as a generalization of the forward sensitivity analysis method used in deterministic systems. We apply the results to examples, including a neural network model.
The influence of antioxidants in the thiyl radical induced lipid peroxidation and geometrical isomerization in micelles of linoleic acid

Abstract The biomimetic model of micelles of linoleic acid containing 2-mercaptoethanol and the antioxidant was examined under gamma irradiation up to 400 Gy in aerobic or deoxygenated conditions where thiyl radicals are the main reactive species. Lipid peroxidation was retarded by ascorbic acid and α-tocopherol, whereas this process was strongly inhibited by resveratrol as effectively as the ascorbic acid/α-tocopherol mixture. Furthermore, antioxidants have a much stronger inhibitory effect on the peroxidation in the presence of 2-mercaptoethanol, and at the same time show protective properties of the double bond, decreasing the cis–trans isomerization. Under anaerobic conditions, cis–trans isomerization occurred and antioxidants efficiency increased along the series: resveratrol < α-tocopherol < ascorbic acid. This result is explained taking into account the double bond localization in the hydrophobic core of the micelle and the need of co-localization of the antioxidant in order to get an anti-isomerizing activity and protection of the natural lipid geometry.
FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs.
Urban dynamics-The first fifty years

This article recounts my own experience in five applications of urban dynamics. The first four applications occurred within a 40-mile radius of M.I. T. -Lowell, Boston, Concord and Marlborough, all in Massachusetts. The fifth transplanted the theory to the Atlantic beaches of Florida and a new community called Palm Coast. All five applications differed from one another. In the first, Lowell, we demonstrated the importance of a limited land resource in shaping urban policy. In Boston, we underscored how urban aging widens the gap between the city’s high-priced job base and its low-priced housing stock. Work in Concord employed simple models to capture the powerful feedback forces that drive migration and growth. Marlborough bypassed formal modeling, using the underlying theory to shape a verbal logic that supported political actions aimed at preserving the older inner neighborhoods in a dynamic equilibrium. Finally, a substantially revised model was constructed to guide the projected 80-year growth of Palm Coast, from a tiny community of 3000 to a new town of 224,000.
TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer.

PURPOSE The identification of patients with metastatic triple-negative breast cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of interest. We conducted a single-arm phase II clinical trial of single-agent platinum for mTNBC with biomarker correlates. PATIENTS AND METHODS Patients with mTNBC received first- or second-line cisplatin (75 mg/m(2)) or carboplatin (area under the concentration-time curve 6) by physician's choice once every 3 weeks. Coprimary end points were objective response rate (RR) and response prediction by p63/p73 gene expression. Secondary and exploratory end points included toxicity assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined subgroups, including BRCA1/2 mutation carriers. RESULTS Patients (N = 86; 69 as first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was 25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%) than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2 mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory analyses showed that a BRCA-like genomic instability signature (n = 32) discriminated responding and nonresponding tumors (mean homologous recombination deficiency-loss of heterozygosity/homologous recombination deficiency-large-scale state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively), whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five of the six long-term responders alive at a median of 4.5 years lacked germline BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores. CONCLUSION Platinum agents are active in mTNBC, especially in patients with germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify patients without mutations who could benefit from platinum therapy agents. Prospective controlled confirmatory trials are warranted.
Neurogenesis in a rat model of age‐related cognitive decline

Age‐related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age‐related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5‐bromo‐2′‐deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU‐positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU‐positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double‐labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.
Changes in S‐adenosylmethionine synthetase in human liver cancer: Molecular characterization and significance

S‐adenosylmethionine synthetase (SAMS) catalyzes the formation of S‐adenosylmethionine (SAM) and is essential to normal cell function. There are two forms of SAMS, liver‐specific and nonliver‐specific (often referred to as “kidney”), which are products of two different genes. SAMS isoenzymes differ greatly in kinetic parameters and sensitivity to inhibition by methionine analogs. The current work studied changes in SAMS and their significance in liver cancer. Northern blot analysis showed that while normal liver expresses only liver‐specific SAMS, both HepG2 and HuH‐7 cells express only nonliver‐specific SAMS. Absence of liver‐specific SAMS messenger RNA (mRNA) was not because of gene deletion or rearrangement but complete lack of gene transcription. Reverse‐transcription polymerase chain reaction (RT‐PCR) with liver‐and kidney‐specific SAMS primers showed that liver‐specific SAMS mRNA was absent with only kidney SAMS mRNA present in HepG2, HuH‐7, Hep3B, and HuH‐1 cells, and four consecutive hepatocellular carcinoma (HCC) specimens. Normal liver tissues from the same patients express both forms of SAMS mRNA. As a result of the change in SAMS expression, SAMS activity was higher in HepG2 and HuH‐7 cells at physiologically relevant methionine concentrations but lower at high (mmol/L) methionine concentrations than rat hepatocytes. Treatment with ethionine and seleno‐D,L‐ethionine, two inhibitors known to have I50 values 50 to 60 times lower against SAMS purified from Novikoff hepatoma cells as compared with SAMS purified from normal rat liver, resulted in increased cell lysis in HepG2 and HuH‐7 cells but not cultured rat hepatocytes. These agents did not affect cellular adenosine triphosphate (ATP) levels but inhibited SAMS activity in HepG2 and HuH‐7 cells when added to their protein extracts. In summary, expression of SAMS is altered in human liver cancer. This occurrence may provide a potentially exploitable target for cancer chemotherapy.
What a Girl Wants?: Fantasizing the Reclamation of Self in Postfeminism

1: Introduction 2: Postfeminism, Family Values, and the Social Fantasy of the Hometown 3: Time Crisis and the New Postfeminist Life Cycle 4: Postfeminist Working Girls: New Archetypes of the Female Labor Market 5: Hyperdomesticity, Self-Care and the Well-Lived Life in Postfeminism
The Allen Telescope Array: The First Widefield, Panchromatic, Snapshot Radio Camera for Radio Astronomy and SETI

The first 42 elements of the Allen Telescope Array (ATA-42) are beginning to deliver data at the Hat Creek Radio Observatory in northern California. Scientists and engineers are actively exploiting all of the flexibility designed into this innovative instrument for simultaneously conducting surveys of the astrophysical sky and conducting searches for distant technological civilizations. This paper summarizes the design elements of the ATA, the cost savings made possible by the use of commercial off-the-shelf components, and the cost/performance tradeoffs that eventually enabled this first snapshot radio camera. The fundamental scientific program of this new telescope is varied and exciting; some of the first astronomical results will be discussed.
On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2* measurements in myocardial siderosis in thalassemia

Magnetic resonance T2* has been validated as a noninvasive means of assessing myocardial iron overload. However, the effect on myocardial T2* of factors such as shimming, variations in capillary geometry, and susceptibility in relation to the effects of iron has not been fully clarified. Since T2 is not affected by extrinsic magnetic field inhomogeneity and has different sensitivity to capillary geometry, investigation into the in vivo relationship between myocardial T2* and T2 measurements can shed light on this important issue. This study was performed in 136 thalassemia patients. The myocardial T2 and T2* thresholds for normality created identical no‐iron‐overload and iron‐overloaded patient groups. In the no‐iron group, there was no correlation between myocardial T2 and T2*. In the iron‐overloaded patients, there was a linear correlation (R2 = 0.89) between myocardial T2* and T2 measurements, which indicates that the iron deposition is the dominant factor in determining these two relaxation values in this scenario. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.
Antiproliferative Compounds from Cleistanthus boivinianus from the Madagascar Dry Forest1

The two new lignans 3α-O-(β-d-glucopyranosyl)desoxypodophyllotoxin (1) and 4-O-(β-d-glucopyranosyl)dehydropodophyllotoxin (2) were isolated from Cleistanthus boivinianus, together with the known lignans deoxypicropodophyllotoxin (3), (±)-β-apopicropodophyllin (4), (−)-desoxypodophyllotoxin (5), (−)-yatein (6), and β-peltatin-5-O-β-d-glucopyranoside (7). The structures of all compounds were characterized by spectroscopic techniques. Compounds 1, 4, and 5 showed potent antiproliferative activities against the A2780 ovarian cancer cell line, with IC50 values of 33.0 ± 3.6, 63.1 ± 6.7, and 230 ± 1 nM, respectively. Compounds 2 and 7 showed only modest A2780 activities, with IC50 values of 2.1 ± 0.3 and 4.9 ± 0.1 μM, respectively, while compounds 3 and 6 had IC50 values of >10 μM. Compound 1 also had potent antiproliferative activity against the HCT-116 human colon carcinoma cell line, with an IC50 value of 20.5 nM, and compound 4 exhibited modest antiproliferative activity against the A2058 human caucasian metastatic melanoma and MES-SA human uterine sarcoma cell lines, with IC50 values of 4.6 and 4.0 μM, respectively.
Junior Army Officer Retention Intentions: A Path Analytic Model

Abstract : This research tests a model of the determinants of retention intentions in a sample of recently commissioned (1984-1987), married, male, junior Army officers. Four variables--perceived Army career prospects, organizational identification, anticipated work/family conflict, and years of services--were specified as direct determinants of propensity to stay in the Army. Five additional variables (person/branch match, prior career orientation, current work satisfaction, operational support, and inspirational leadership) were hypothesized to have indirect effects on retention, operating through their influence on career prospects and identification. The predictions of the model were largely supported. Organizational identification had strong positive effects, and work/family conflict had strong negative effects on propensity to stay. Perceived career prospects and years of service also had significant, although smaller, positive effects. In combination, the direct determinants accounted for half of the variance in the dependent variable. Of the four antecedent variables predicted to influence Army career prospects, three had significant path coefficients (branch match, work satisfaction, and operational support received). All three variables hypothesized to affect organizational identification were significant (prior orientation toward a military career, operational support, and inspirational leadership), but they explained little (18%) of the variance in identification.
Effect of temocillin in combination with other beta-lactam antibiotics

The antibacterial interactions of temocillin with other beta-lactams were tested by checkerboard combination in Mueller-Hinton agar against 146 strains of members of the family Enterobacteriaceae, 35 Pseudomonas aeruginosa strains, and 35 Staphylococcus aureus strains. Most combinations showed a moderate degree of synergism. In only one Klebsiella strain was minor antagonism observed between temocillin and ampicillin.
Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion

The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more remarkable. Predictive factors for successful ocriplasmin treatment were identified for VMT (VMA diameter smaller than 1,500 μm) and MH (smaller than 250 μm). In comparison with the highly predictable outcome after vitrectomy, the general success rate of ocriplasmin not under clinical trial conditions has not fully met expectations and needs to be proven in real-world clinical settings. The ocriplasmin data will be compared in the future with observational data on spontaneous VMA release, will help retina specialists make more accurate predictions, and will improve outcome rates.
Value of histochemical reactions for mucosubstances in the diagnosis of certain pathological conditions of the colon and rectum.

Thehistopathologist quite often faces diagnostic problems suchastherecognition ofearly stages of disease, borderline cases, and morphologically atypical pictures which arenotalways solved bythe usuallaboratory techniques. Recenthistochemical advances inidentifying different classes ofmucosubstances givemoretools whichcanusefully be applied tosolve someofthese diagnostic difficulties. Otherauthors working inthis field havealready shownthevalueofthese techniques notonlyfor diagnostic purposes butalso fortheunderstanding of thephysiological processes inhumansecretory epithelia andtheir variations indisease (Lev, 1966; Tellem, Nedwich, Amenta,andImbriglia, 1966; Greco, Lauro, Fabbrini, andTorsoli, 1967; Hukill andVidone, 1967; Esterly andSpicer, 1968). Byapplying avariety ofhistochemical techniques tosomepathological conditions ofthecolonand rectum anattempt hasbeenmadetodrawamapof themucosubstances present indifferent diseases and tofind a'trait' whichcouldbeanaidtomorphological diagnosis. MATERIALAND METHODS
Risk of Developing Fibroadenoma with the Use of Cyclosporine A in Renal Transplant Recipients

To investigate the effect of cyclosporine A (Cyc A) on the development of fibroadenomas, 30 renal transplant patients and 20 chronic renal failure patients on dialysis were breast examined with ultrasonography and/or mammography. Of the renal transplant patients, 17 were receiving Cyc A-based combination therapy for immunosuppression. All patients were female with the age range of 29.7 ± 9.2 years in the transplant group and 33.95 ± 9.91 in the dialysis group. Eight of the 17 patients receiving Cyc A had fibroadenomas, 5 of them having bilateral lesions. None of the other patients, those on dialysis and on non-Cyc A combination therapy had fibroadenomas. A significant difference for fibroadenoma incidence in patients receiving Cyc A combination immunosuppression was found.
The Dynamic Interplay between Appraisal and Core Affect in Daily Life

Appraisals and core affect are both considered central to the experience of emotion. In this study we examine the bidirectional relationships between these two components of emotional experience by examining how core affect changes following how people appraise events and how appraisals in turn change following how they feel in daily life. In an experience sampling study, participants recorded their core affect and appraisals of ongoing events; data were analyzed using cross-lagged multilevel modeling. Valence-appraisal relationships were found to be characterized by congruency: the same appraisals that were associated with a change in pleasure-displeasure (motivational congruency, other-agency, coping potential, and future expectancy), changed themselves as a function of pleasure-displeasure. In turn, mainly secondary appraisals of who is responsible and how one is able to cope with events were associated with changes in arousal, which itself is followed by changes in the future appraised relevance of events. These results integrate core affect and appraisal approaches to emotion by demonstrating the dynamic interplay of how appraisals are followed by changes in core affect which in turn change our basis for judging future events.
Isolation of ribosome containing synaptosome subpopulation with active in vitro protein synthesis

Subpopulations of synaptosomes harvested from neonatal rat brain cortices revealed a differential ability to synthesize protein in vitro. Incubation of synaptosomes with radiolbeled leucine, followed by continuous sucrose gradient centrifugation produced an asymmetric shift in the radioactivity toward the higher density sucrose fractions. The bulk of the mitochondrial cytochrome c‐oxidase activity was also found in these fractions, however, subfractionation studies of osmotically‐lysed synaptosomes suggested that the newly‐synthesized proteins reside in an osmotically sensitive, non‐mitochondrial compartment.