Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel anti‐fatty acid synthase compounds with anti‐cancer activity in HER2+ breast cancer

Fatty acid synthase (FASN) expression and activity has emerged as a common phenotype in most human carcinomas, including breast cancer, and its expression is tightly linked to HER2 signaling pathways. The development of inhibitors of FASN activity has consequently appeared as a novel antitarget modality for treating cancer. However, the clinical use of FASN inhibitors, such as cerulenin, C75, and epigallocatechin 3‐gallate (EGCG), is limited by anorexia and induced body weight loss or by its low in vivo potency and stability. Here, we summarize the design and development of G28UCM, the lead‐compound of a novel family of synthetic FASN inhibitors, with both in vitro and in vivo activity in a human breast cancer model of FASN+ and HER2+.
Adaptive BVH: an evaluation of an efficient shared data structure for interactive simulation

The strive towards realistic simulations at interactive speeds has driven research in both rendering and physical simulation. This heightened realism involves larger data sets and data structures, and comes at a high computational cost. We investigate simulations involving collision detection and real-time ray-tracing and note similarities in the data structures used to accelerate them. Our investigation demonstrates that it is possible to utilize a single Acceleration Data Structure (ADS) for both subsystems of an interactive simulation, even though they benefit from different characteristics. Typically, the collision detection and ray-tracing system build ADSs that satisfy their specific needs. We argue for a shared adaptive ADS that can be optimized for both collision detection and ray-tracing. The collision detection system builds this adaptive ADS and the ray-tracing algorithm uses the same adaptive ADS after the collision detection system has resolved potential collisions, therefore saving memory, execution time and power. The results show that compromises need not be made on build heuristics. Furthermore, the ADS may be optimized for primary and secondary rays and consequently save more memory, execution time and large quantities of power.
Similar cell surface expression of beta2-microglobulin-free heavy chains by HLA-B27 subtypes differentially associated with ankylosing spondylitis.

OBJECTIVE To determine whether the cell surface features of HLA-B27 subtypes reported to be differentially associated with ankylosing spondylitis (AS) differ in a way that correlates with disease susceptibility. METHODS Human cell transfectants expressing or lacking the transporter associated with antigen processing were used to determine the cell surface expression of B27 subtypes by flow cytometry with antibodies recognizing the B27 heterodimer or beta2-microglobulin (beta2m)-free heavy chains. RESULTS In lymphoid cells with an intact peptide-loading complex, all B27 subtypes, irrespective of their association with disease, showed similar ratios of free heavy chain to heterodimer, suggesting similar surface stability. A substantial decrease in dissociated heavy chains, which never reached 100%, was observed upon addition of a B27 ligand, with no significant differences among subtypes. This is compatible with similar surface expression of irreversible beta2m-free heavy chain forms among subtypes differentially associated with disease. In cells lacking the transporter associated with antigen processing, both disease-associated and non-disease-associated subtypes expressed a population of heterodimers at 26 degrees C that was less stable than the population expressed at 37 degrees C. In the presence of exogenous peptide, the expression of heterodimers increased, without a concomitant decrease in beta2m-free heavy chains. This suggests that in these cells, and for all subtypes tested, most of the dissociated heavy chains at the cell surface are in irreversible forms. At 37 degrees C, the expression of beta2m-free B27 heavy chains was very low on T2 transfectant cells. CONCLUSION HLA-B27 subtypes showing differential associations with AS are similar in their extent of beta2m dissociation and surface expression of free heavy chains.
The combination of a novel 2 bp deletion mutation and p.D63H in CYP11B1 cause congenital adrenal hyperplasia due to steroid 11β-hydroxylase deficiency.

Deficiency of steroid 11β-hydroxylase activity occurs in 5-8% of patients with congenital adrenal hyperplasia (CAH). The aim of the current study was to identify mutations in the CYP11B1 gene of a patient with CAH due to deficiency of steroid 11β-hydroxylase activity, and to study the functional and structural consequences of these mutations. A molecular genetic analysis of the CYP11B1 gene in this patient and her parents identified a known missense mutation g.5194G>C (p.D63H) and a novel 2 bp deletion mutation (g.9525_9526delCT, corresponding to p.L380V…R420X) in the patient. In vitro expression studies in COS7 cells revealed a decreased 11β-hydroxylase activity in the p.D63H mutant to 2.0±0.8% and in the p.L380V…R420X mutant to 0.2±2.2% for the conversion of 11-deoxycortisol to cortisol. Three dimensional homology models for the normal and mutant proteins were built by using the recently published x-ray structure of the human CYP11B2 as a template. Presumably, the g. 9525_9526delCT mutation in CYP11B1 resulted in a truncated protein with a misfolded C-terminal domain that could not efficiently bind heme iron, substrate, and adrenodoxin and had lost its biochemical function. In summary, CAH due to steroid 11β-hydroxylase deficiency can be attributed to both the novel deletion mutation (g.9525_9526delCT, corresponding to p.L380V…R420X) and known missense mutation (g.5194G>C corresponding to p.D63H) in CYP11B1.
Work transitions and health in later life.

OBJECTIVES The goal of the analysis was to examine the association between health status and work behavior among men aged 55-69. We specifically examined the conditions under which health is most strongly associated with labor force exit and reentry. METHODS The association between health and labor force transitions was examined using logistic regression analyses, based on data from the 1984 and 1985 panels of the Survey of Income and Program Participation. RESULTS We found that for men aged 55-69 in the mid-1980s, poor health was positively associated with labor force exit, and negatively associated with returns to work. Although these main effects are very strong, we found that health was particularly important among individuals for whom retirement was least attractive. Health had its most substantial association with work transitions among men with working wives, as well as among men who were younger, or who had limited nonwork financial resources. Health also had a particularly strong association with work transitions among Black men, but only with reference to reentry decisions. DISCUSSION Our results suggest that continued work may have limited appeal for men who are prepared for retirement, even when they are in excellent health.
Forecasting Liquidity Ratio of Commercial Banks in Nigeria

In this paper, autoregressive fractionally integrated moving average (ARFIMA) model was proposed and was used for modeling and forecasting of liquidity ratio of commercial banks in Nigeria. Augmented Dickey Fuller (ADF) test was used for testing stationarity of the series. The long lasting autocorrelation function of the data showed the presence of long memory structure, and the Hurst exponent test was used to test for presence of long memory structure. The Geweke and Porter-Hudak (GPH) method of estimation was used to obtain the long memory parameter d of the ARFIMA model. Alternatively, a suitable ARIMA model was fitted for the liquidity ratio data. On the basis of minimum AIC values, the best model was identified for each of ARFIMA and ARIMA models respectively. The models were specified as ARFIMA(5,0.12,3) and ARIMA(1,1,1). To this end, forecast evaluation for the two models were carried out using root mean square error (RMSE). Having compared the forecasting result of the two models, we concluded that the ARFIMA model was a much better model in this regard.
On Achieveing Bandwidth-Aware LSP//spl lambda/SP Multiplexing/Separation in Multi-layer Networks

We present a new traffic engineering (TE) model which is based on QoS rerouting and uses hybrid resilience to improve the recovery performance of multi-layer networks where an MPLS network is layered above an MPlambdaS network. We formulate the rerouting of the LSPs/lambdaSPs as a multi-constrained problem and use its polynomial reduction to find a heuristic solution that can be implemented by standardized constraint-based routing algorithms. This heuristic solution uses a cost-based routing optimization to achieve different network configurations which multiplex/separate bandwidth-aware LSPs/lambdaSPs on the network links. We formulate the resilience upon failure as a multi-objective problem consisting of finding a resilience strategy that minimizes recovery operation time and maximizes the LSP/lambdaSP restorability. A solution to this problem is proposed where a hybrid resilience framework is used to achieve restoration in the MPLS layer to complement path switching in the MPlambdaS layer. We evaluate the performance of the TE model when rerouting the tunnels carrying the traffic offered to a 23- and 31-node networks. Simulation reveals that the hybrid resilience model performs better than classical recovery mechanisms. In terms of restorability, quality of rerouting paths and rerouting stability
A Myocutaneous Latissimus Dorsi Propeller Flap Based on a Single Dorsal Intercostal Perforator

Summary: This study presents a novel surgical technique for the reconstruction of highly challenging large lower back defects. In this case, a 72-year-old man initially diagnosed with renal cell carcinoma received nephrectomy followed by the dissection of an iliac crest metastasis and repeated high-dose irradiation therapy. Several years later, an osteocutaneous fistula at the right caudal posterior trunk made the reconstruction of the lower back defect necessary. High-dose irradiation of the lower back and poor vascular conditions at the pelvic region disqualified the patient for previously published local or free flap options. The initial strategy of an arteriovenous loop anastomosed to the femoral vessels and a free latissimus dorsi flap transfer had to be withdrawn due to repeated intraoperative loop thrombosis. For that reason, the entire latissimus dorsi muscle was used as a myocutaneous propeller flap receiving its blood supply solely through a single dorsal intercostal artery perforator. The flap survived completely and no fistulous formation occurred postoperatively. The time to complete wound healing was 4 months. This new technique is considered a valuable addition for the reconstruction of challenging posterior caudal trunk defects.
The action of serotonin in the rat hippocampal slice preparation.

1. Intracellular activity was recorded from neurones in the CA1 pyramidal layer of slices of rat hippocampus maintained in vitro. 2. Application of 5‐HT in a droplet or via ionophoresis produced a 3‐5 mV hyperpolarization associated with a 30% decrease in input resistance. 3. The response to 5‐HT was minimal with a drop concentration of 1 microM and maximal with 100 microM. The responses appeared to be blocked by methysergide applied in the superfusion medium. 4. The responses to 5‐HT were minimal when the drug was applied in the apical dendritic region and maximal when it was applied near the soma. 5. 5‐HT produced no substantial changes in e.p.s.p.s evoked by stimulation of the Schaffer collateral‐commissural system or in i.p.s.p.s which were occasionally encountered following stimuli to the stratum radiatum. 6. The responses to 5‐HT are true post‐synaptic responses and are not indirect effects since they are present in a Ca2+‐deficient Mg2+‐enriched medium which blocks synaptic transmission. 7. The responses to 5‐HT were not dependent on extracellular Cl‐ concentration. 8. These experiments indicate that 5‐HT produces its effects in the rat hippocampus by activating K+ channels.
R ADIAL VARIATION IN WOOD SPECIFIC GRAVITY OF TROPICAL TREE SPECIES DIFFERING IN GROWTH – MORTALITY STRATEGIES 1

(cid:129) Premise of the study: Wood speciﬁ c gravity (WSG) mediates an interspeciﬁ c trade-off between growth and mortality and is a key measure for estimating carbon stocks. Most studies use species mean values to represent WSG, despite variation at different levels of biological organization. We examined sources of variation in WSG across four nested scales (segments within cores, cores within trees, trees within species, and species), compared the pattern of radial variation in WSG among species differing in growth strategies, and investigated the effect of WSG radial variation on aboveground biomass estimates. (cid:129) Methods: We took two perpendicular cores from six individuals each of 20 tropical tree species representing a broad range of mean WSGs and growth–mortality strategies in a lowland tropical moist forest in Panama. Cores were divided into 1-cm segments, and WSG was determined for each segment. (cid:129) Key results: The bulk of the total variance in WSG was dominated by interspecies variation (88%), whereas variation due to measurement error, segments within cores, and cores within trees (8%) was minimal. Radial variation in WSG, deﬁ ned as change in WSG with increasing distance from the pith, was signiﬁ cant in 17 of the 20 species and included signiﬁ cant monotonic increases in 6 species and nonmonotonic patterns in 11 species. Radial variation in WSG resulted in a small but signiﬁ cant bias in aboveground biomass estimates. (cid:129) Conclusions: Radial variation in WSG is related to a species’ growth strategy and, though minimal compared with interspeciﬁ c variation in WSG, can cause a downward bias when not incorporated into aboveground biomass estimates.
Detection and staging of dementia in Alzheimer's disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer's Disease.

Our earlier studies using the Consortium to Establish a Registry of Alzheimer's Disease neuropsychological battery showed that delayed recall was a highly sensitive indicator of early Alzheimer's disease. None of the learning and memory measures in the battery were found to be useful in staging the severity of this form of dementia. This study explores the nonmemory functions (fluency, naming, and praxis) of the Consortium to Establish a Registry of Alzheimer's Disease battery and asks whether performance on any of these measures adds to the detection of early Alzheimer's disease or is sensitive to the later progression of the illness. We stratified patients with this disease according to severity (mild, moderate, severe), and compared them with age-, education-, and gender-matched control subjects (group N = 49 each). Multivariate procedures and cutting scores were used to determine the efficacy of the various measures in distinguishing between the cases and control subjects. Impairment of delayed recall was again found to be the best discriminator for detecting mild cases of Alzheimer's disease. Confrontation naming was the only nonmemory factor that assisted in this discrimination. For staging the illness, a combination of measures including fluency, praxis, and recognition memory best differentiated cases with mild dementia from those with either moderate or severe stages of disease. Measures of delayed recall quickly "bottomed out" in the patients with Alzheimer's disease and proved of little value in staging the disorder. (ABSTRACT TRUNCATED AT 250 WORDS)
Surveillance for occupational asthma--Michigan and New Jersey, 1988-1992.

PROBLEM/CONDITION A case of occupational asthma is a sentinel health event indicating a need for preventive intervention. REPORTING PERIOD COVERED 1988-1992. DESCRIPTION OF SYSTEMS As part of the Sentinel Event Notification System for Occupational Risks (SENSOR) Program, initiated by CDC's National Institute for Occupational Safety and Health in 1987, state-based surveillance and intervention programs for occupational asthma (OA) have been under development in Michigan and New Jersey. The initial 5-year projects in these states have been completed. RESULTS From 1988 through 1992, the SENSOR programs in these states identified a total of 535 cases of occupational asthma and related conditions. Of these 535 cases, 328 cases met the SENSOR surveillance case definition for OA. In addition, 128 cases were classified as possible OA, 42 as reactive airways dysfunction syndrome, and 37 as occupationally aggravated asthma. In both Michigan and New Jersey, manufacturing was the industrial sector with the largest proportion of cases. In Michigan, > 40% of the case-patients worked in transportation equipment manufacturing. In New Jersey, 15% of case-patients worked in manufacturing of chemicals and allied products. Overall, isocyanates were the most frequently reported asthma-causing agents (19.4% of cases). Follow-up industrial hygiene sampling measured suspect agents at airborne concentrations generally below the permissible exposure limits established by the Occupational Safety and Health Administration. INTERPRETATION In its first 5 years, the SENSOR system has led to the identification of previously unrecognized causes of occupational asthma. Overall findings indicate the need for more comprehensive control of such well-known occupational allergens as the isocyanates. In addition, SENSOR interventions have prompted improvements in protection for workers. ACTIONS TAKEN Approaches to state-based surveillance and intervention for OA are being developed through newly funded 5-year SENSOR projects in four states (California, Massachusetts, Michigan, and New Jersey). The goal is to develop a model for effective state-based OA surveillance that can be applied by any state health department.
The meaning of slow nursing in dementia care

Research literature in the dementia field lacks examples of ‘best-practices’ demonstrating concretely how it is possible to support the sense of coherence in people with dementia. The purpose of this study was to elucidate the nurses’ views concerning a caring approach that may support the sense of coherence in people with dementia. The data were collected through participant observation and focus group interviews during a four-month period in 2011. Sixteen registered nurses recruited from two Norwegian nursing homes participated in this study. The data were interpreted using a phenomenological-hermeneutical method. Three themes were identified: ‘being in the moment’, ‘doing one thing at a time’, and ‘creating joy and contentment’. An overall interpretation of these themes is described by the metaphor ‘slow nursing’, a caring approach that may lead to supporting the sense of coherence in people with dementia.
Mesoporous Silica Nanoparticles: A Potential Inorganic Filler to Prepare Polymer Composites with Low CTE and Low Modulus for Electronic Packaging Applications

For electronic packaging applications, polymer based SiO2 composites with low CTE and low elastic modulus are of great importance to the thermal or mechanical stress relief and reliability improvement. However, it's still a great challenge to achieve these goals simultaneously by incorporating conventional SiO2 filler into resin matrix. In this study, we prepared the mesoporous SiO2 filler through a modified Stöber approach and then comparatively investigated the viscosities and thermomechanical performance such as modulus, glass transition temperature (Tg) and CTE, etc. of composites filled with mesoporous and nonporous SiO2 filler. The results showed the mesoporous SiO2 fillers was more effective to lower the CTE values as compared with spherical SiO2 fillers without mesopores. It means that much lower SiO2 loading is needed to achieve a desired CTE value using mesoporous silica as fillers and thus the modulus of obtained composites can be controlled at a lower level. Therefore, our results provide an effective approach to overcome the conflicting requirements between the low CTE and low modulus of polymer based composites. Besides, compared with nonporous SiO2 composites, mesoporous SiO2 composites exhibit higher transparency, higher Tg and higher adhesive strength, which makes mesoporous SiO2 a promising filler for electronic packaging applications.
Exercises for paretic upper limb after stroke: a combined virtual-reality and telemedicine approach.

OBJECTIVE Telerehabilitation enables a remotely controlled programme to be used to treat motor deficits in post-stroke patients. The effects of this telerehabilitation approach were compared with traditional motor rehabilitation methods. DESIGN Randomized single-blind controlled trial. PATIENTS A total of 36 patients with mild arm motor impairments due to ischaemic stroke in the region of the middle cerebral artery. METHODS The experimental treatment was a virtual reality-based system delivered via the Internet, which provided motor tasks to the patients from a remote rehabilitation facility. The control group underwent traditional physical therapy for the upper limb. Both treatments were of 4 weeks duration. All patients were assessed one month prior to therapy, at the commencement and termination of therapies and one month post-therapy, with the Fugl-Meyer Upper Extremity, the ABILHAND and the Ashworth scales. RESULTS Both rehabilitative therapies significantly improved all outcome scores after treatment, but only the Fugl-Meyer Upper Extremity scale showed differences in the comparison between groups. CONCLUSION Both strategies were effective, but the experimental approach induced better outcomes in motor performance. These results may favour early discharge from hospital sustained by a telerehabilitation programme, with potential beneficial effects on the use of available resources.
A Plant-specific Cyclin-dependent Kinase Is Involved in the Control of G2/M Progression in Plants*

Cyclin-dependent kinases (CDKs) control the key transitions in the eukaryotic cell cycle. All the CDKs known to control G2/M progression in yeast and animals are distinguished by the characteristic PSTAIRE motif in their cyclin-binding domain and are closely related. Higher plants contain in addition a number of more divergent non-PSTAIRE CDKs with still obscure functions. We show that a plant-specific type of non-PSTAIRE CDKs is involved in the control of the G2/M progression. In synchronized tobacco BY-2 cells, the corresponding protein, accumulated in a cell cycle-regulated fashion, peaking at the G2/M transition. The associated histone H1 kinase activity reached a maximum in mitosis and required a yet unidentified subunit to be fully active. Down-regulation of the associated kinase activity in transgenic tobacco plants using a dominant-negative mutation delayed G2/M transition. These results provide the first evidence that non-PSTAIRE CDKs are involved in the control of the G2/M progression in plants.