Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential impact of RB status on E2F1 reprogramming in human cancer

The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease. While RB loss was associated with lethal disease, RB-deficient tumors had no proliferative advantage and exhibited downstream effects distinct from cell cycle control. Mechanistically, RB loss led to E2F1 cistrome expansion and different binding specificity, alterations distinct from those observed after functional RB inactivation. Additionally, identification of protumorigenic transcriptional networks specific to RB loss that were validated in clinical samples demonstrated the ability of RB loss to differentially reprogram E2F1 in human cancers. Together, these findings not only identify tumor-suppressive functions of RB that are distinct from cell cycle control, but also demonstrate that the molecular consequence of RB loss is distinct from RB inactivation. Thus, these studies provide insight into how RB loss promotes disease progression, and identify new nodes for therapeutic intervention.
Estimating Biomass of Native Grass Grown under Complex Management Treatments Using WorldView-3 Spectral Derivatives

The ability of texture models and red-edge to facilitate the detection of subtle structural vegetation traits could aid in discriminating and mapping grass quantity, a challenge that has been longstanding in the management of grasslands in southern Africa. Subsequently, this work sought to explore the robustness of integrating texture metrics and red-edge in predicting the above-ground biomass of grass growing under different levels of mowing and burning in grassland management treatments. Based on the sparse partial least squares regression algorithm, the results of this study showed that red-edge vegetation indices improved above-ground grass biomass from a root mean square error of perdition (RMSEP) of 0.83 kg/m2 to an RMSEP of 0.55 kg/m2. Texture models further improved the accuracy of grass biomass estimation to an RMSEP of 0.35 kg/m2. The combination of texture models and red-edge derivatives (red-edge-derived vegetation indices) resulted in an optimal prediction accuracy of RMSEP 0.2 kg/m2 across all grassland management treatments. These results illustrate the prospect of combining texture metrics with the red-edge in predicting grass biomass across complex grassland management treatments. This offers the detailed spatial information required for grassland policy-making and sustainable grassland management in data-scarce regions such as southern Africa.
Infrared Transmission Spectra for Extrasolar Giant Planets

Among the hot Jupiters known to date that transit their parent stars, the two best candidates to be observed with transmission spectroscopy in the mid-infrared (MIR) are HD 189733b and HD 209458b, due to their combined characteristics of planetary density, orbital parameters, and parent star distance and brightness. Here we simulate transmission spectra of these two planets during their primary transit in the MIR, and we present sensitivity studies of the spectra to the changes of atmospheric thermal properties, molecular abundances, and C/O ratios. Our model predicts that the dominant species absorbing in the MIR on hot Jupiters are water vapor and carbon monoxide, and their relative abundances are determined by the C/O ratio. Since the temperature profile plays a secondary role in the transmission spectra of hot Jupiters compared to molecular abundances, future primary transit observations in the MIR of those objects might offer insight on extrasolar giant planet atmospheric chemistry. We find here that the absorption features caused by water vapor and carbon monoxide in a cloud-free atmosphere are deep enough to be observable by the present and future generation of space-based observatories, such as Spitzer Space Telescope and James Webb Space Telescope. We discuss our results in light of the capabilities of these telescopes.
Improving fatty acids production by engineering dynamic pathway regulation and metabolic control

Significance One important synthetic chemistry reaction endowed by nature is the decarboxylative carbon condensation reaction using malonyl-CoA as carbon donor. Previous metabolic engineering efforts centered on the malonyl-CoA–dependent pathway have resulted in the production of many value-added compounds. Here we mimicked the native biological systems and used a dynamic regulatory network to optimize production titers and yield. The naturally existing transcriptional regulator FapR was rewired to dynamically control gene expressions involved in the supply and consumption of malonyl-CoA. Applying this metabolic control allowed the engineered cell to dynamically regulate pathway expression and compensated the metabolic activity of critical enzymes. The synthetic malonyl-CoA switch engineered in this study opens up new venues for dynamic pathway optimization and efficient production of malonyl-CoA–derived compounds. Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA–derived compounds.
Hydroxyoximes and Copper Hydrometallurgy

Development of Hydrometallurgical Processes. Industrial Hydroxyoxime Extractants and Their Characteristics. Physicochemistry of Metal Extraction with Hydroxyoximes. Potential of Metal Extraction and Separation with Hydroxyoximes. Application of Hydroxyoximes in Membrane Processes. Processing of Copper Ores. Index.
Introspection Mechanisms for Semi-Formal Verification in a System-Level Design Environment

A new generation of CAD tools is mandatory to cope with the growing complexity of system-on-chip. We believe that they should be built on top of a modern and standard framework. ESys.NET is a design environment based on the . NET framework. It takes advantage of advanced programming features which facilitates the integration of external tools. This paper presents a semi-formal verification tool for ESys.NET. Introspection ability is emphasized together with its capabilities to cooperate with third party tools. Introspection is used to retrieve the state of the model during simulation and to check a set of user defined rules. Neither the model nor the simulator is modified by the verification process. Experimentations on an AMBA bus model highlight the effectiveness of this approach
Review of recent efforts on the growth and characterization of nitride-based diluted magnetic semiconductors

Wide bandgap nitrides and oxides have been heralded as a possible platform for future semiconductor spintronics applications based on the inherent compatibility of these materials with existing semiconductors as well as theoretical predictions of room temperature ferromagnetism. Experimental reports of room temperature ferromagnetism in these materials are complicated by disparate crystalline quality and phase purity in these materials, as well as conflicting theoretical predictions as to the nature of ferromagnetic behavior in this system. A complete understanding of these materials, and ultimately intelligent design of spintronic devices, will require an exploration of the relationship between the processing techniques, resulting transition metal atom configuration, defects, and electronic compensation as related to the structure, magnetic, and magneto-optical properties of this material. This work explores the growth and properties of Ga1-xMnxN films by metalorganic chemical vapor deposition on cplane sapphire substrates with varying thickness, Mn concentration, and alloying elements. Homogenous Mn incorporation throughout the films was verified with Secondary Ion Mass Spectroscopy (SIMS), and no macroscopic second phases were detected using X-ray diffraction (XRD). SQUID and vibrating sample magnetometry measurements showed an apparent room temperature ferromagnetic hysteresis, whose strength can be altered considerably through annealing and introduction of either Si or Mg during the growth process. Three sets of Raman modes appeared to be sensitive to Mn incorporation. The intensities of a broad band around 300cm-1 and sharper modes near 669cm-1 increased with increasing Mn concentration. The rise of the former is attributed to a decrease in long-range lattice ordering for higher Mn concentration. The second mode is due to nitrogen vacancy-related local vibrational modes of the GaN host lattice. Si co-doped Ga1-xMnxN results in shallow donor states in GaN suppress the formation of nitrogen vacancies by compensating the p-type deep level defects introduced by substitutional Mn. The formation of a Mn-related midgap impurity band is observed via optical transmission measurement in Ga1-xMnxN with strong magnetic signatures, but not for Si co-doped samples. Initial studies on light emitting diodes (LEDs) containing a Mn-doped active region have also been produced. Devices were fabricated with different Mn-doped active layer thicknesses, and I-V characteristics show that the devices become highly resistive as thickness of the Mn-doped active layer increases. The electroluminescence of these devices is dominated by a high suppressed band-edge recombination and a midgap defect-related emission, leading to an orange-colored but weakly emitting LED. These results suggest that traditional theoretical and device approaches akin to those realized in Ga1-xMnxN may be difficult to realize in Ga1-xMnxN, and exploitation of these materials will require further novel device approaches taking into account the nature of this material.
Parasitic Capacitance Analytical Model for Sub-7-nm Multigate Devices

In this paper, we propose an analytical model to accurately evaluate the parasitic capacitances of an advanced 7-nm-node multigate device structure: 1) FinFET on Silicon On Insulator (SOI) (FFSOI) and 2) stacked nanowire on SOI (SNWSOI). Our model, validated through 3-D TCAD simulations, accounts for gate contact, advanced process bricks, such as gate last, BAR contact, and low-$k$ spacer, but also multilayer dielectric by introducing an equivalent permittivity. Finally, FFSOI and SNWSOI architectures are compared from this parasitic capacitance point of view.
Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study.

OBJECTIVE Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. METHODS A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. RESULTS Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. CONCLUSION This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.
Why Do Worker-Firm Matches Dissolve?

In a dynamic labor market worker-firm matches dissolve frequently causing workers to separate and firms to look for replacements. A separation may be initiated by the worker (a quit) or the firm (a layoff), or may result from a joint decision. A dissolution of a worker-firm match may be inefficient if it can be prevented by wage renegotiation. In this paper we study worker separations in the Dutch labor market. From an analysis of matched worker-firm data we conclude that both quits and layoffs are less likely to occur in high quality matches. We also find that workers with a high propensity to quit are offered higher wages to prevent them to quit. Similarly, workers with a high layoff probability give up some of their wage to prevent them from being laid-off. Despite these wage renegotiations some inefficiency in separations remains. However, there is a clear difference between quits and layoffs. Whereas inefficient quits are rare, inefficient layoffs occur frequently. These phenomena may be related to downward wage rigidity. While it is easy to renegotiate higher wages to prevent quits, it is much more difficult to renegotiate lower wages to prevent layoffs even if that would overall be beneficial to the workers involved.
Vam2/Vps41p and Vam6/Vps39p Are Components of a Protein Complex on the Vacuolar Membranes and Involved in the Vacuolar Assembly in the Yeast Saccharomyces cerevisiae*

The VAM2/VPS41 and VAM6/VPS39 were shown to encode hydrophilic proteins of 113 and 123 kDa, respectively. Deletion of the VAM2 and VAM6 functions resulted in accumulation of numerous vacuole-related structures of 200-400 nm in diameter that were much smaller than the normal vacuoles. Loss of functions of Vam2p and Vam6p resulted in inefficient processings of a set of vacuolar proteins, including proteinase A, proteinase B, and carboxypeptidase Y (CPY), and in severely defective maturation of another vacuolar protein, alkaline phosphatase. A part of newly synthesized CPY was missorted to the cell surface in the mutants. Epitope-tagged versions of Vam2p and Vam6p retained their functions, and they were found mostly in sedimentable fractions. The epitope-tagged Vam2p and Vam6p remained in the sedimentable fractions in the presence of Triton X-100, but they were extracted by urea or NaCl. Vam2p and Vam6p were cross-linked by the treatment of a chemical cross-linker. These observations indicated that Vam2p and Vam6p physically interact with each other and exist as components of a large protein complex. Vam6p fused with a green fluorescent protein were highly accumulated in a few specific regions of the vacuolar membranes. Large portions of Vam2p and Vam6p were fractionated into a vacuolar enriched fraction, indicating that they were localized mainly in the vacuolar membranes. These results showed that Vam2p and Vam6p execute their function in the vacuolar assembly as the components of a protein complex reside on the vacuolar membranes.
A phase I clinical trial of dose escalation of lobaplatin in combination with fixed-dose docetaxel for the treatment of human solid tumours that had progressed following chemotherapy

In this study, the maximum tolerated dose (MTD) of lobaplatin (LBP) when it was combined with docetaxel (TXT) for the treatment of solid tumours that had progressed following chemotherapy was determined, and toxicities to this regimen were evaluated. A modified Fibonacci method was used for the dose escalation of LBP. The patients received TXT (at a fixed dose of 60 mg/m2) on day one (d1) and LBP (at an initial tested dose of 30 mg/m2) on day two (d2) of a treatment cycle that was repeated every 21 days. Each dose group consisted of at least three cases. In the absence of dose-limiting toxicity (DLT), we proceeded to the next dose group, with a dose increment of 5 mg/m2 between groups, until DLT occurred. The dose immediately below the dose that produced DLT was regarded as the MTD. The 17 patients examined in this study completed a total of 58 cycles of chemotherapy, and a total of three dose-escalation groups (30 mg/m2 LBP, 35 mg/m2 LBP, and 40 mg/m2 LBP) were established. The main adverse event that was observed was myelosuppression. DLT occurred in four patients, including three patients in the 40 mg/m2 LBP group and one patient in the 35 mg/m2 LBP group. In total, three out of the four patients in the 40 mg/m2 LBP group exhibited DLT. We determined that the treatment administered to the 35 mg/m2 LBP group represented the MTD. Thus, our phase I trial revealed that the MTD for the tested LBP combination regimen was 35 mg/m2 LBP and 60 mg/m2 TXT. This regimen resulted in mild adverse reactions and favourable patient tolerance. Therefore, we recommend the use of these dosages in phase II clinical trials.
3D NUMERICAL SIMULATIONS OF WAVES GENERATED BY SUBAERIAL MASS FAILURES: APPLICATION TO LA PALMA CASE

Three-dimensional (3D) waves generated by landslides are simulated using a three-fluid Navier-Stokes VOF model. With this approach, the interaction between slide and water is implicitly solved. The model capabilities are first tested for benchmark cases featuring rigid body motion. Results are good in two dimensions (2D) and encouraging in 3D. Wave generation by a potential collapse of the Cumbre Vieja Volcano, on La Palma island, is then studied. Stability analyses show that the Cumbre Vieja flank is currently highly stable and that potential slide volumes are likely to be closer to 100 km, rather than the 500 km predicted in earlier studies. Results of the Navier-Stokes model show that waves generated are highly dependent upon the details of slide mechanism and kinematics. In our worst 3D scenario (assuming an inviscid fluid), the initial wavelength is 20 km and the wave height decrease due to lateral spreading is high.
Child Sexual Abuse Evaluations: Adherence to Recommendations

ABSTRACT Sixty-eight parents of children with alleged child sexual abuse (CSA) were surveyed 4 months after visiting an interdisciplinary CSA evaluation clinic in order to examine the extent to which recommendations were recalled and implemented. Of those parents for whom specific recommendations were provided, 9% recalled recommendations for medical follow-up, 79% recalled recommendations for child therapy, and 43% recalled recommendations for parental therapy. Families were more likely to receive and adhere to recommendations when there were behavioral problems and a strong indication of CSA. To improve communication with families, the reasons for recommendations must be clearly conveyed, and possible barriers to implementation should be anticipated and addressed. In addition, recommendations need to be realistic, and professionals need to facilitate the implementation of their treatment plan.
Comparative study: Efficacy and tolerability of vildagliptin vs. pioglitazone as an add therapy to metformin in poorly controlled type 2 diabetes mellitus patients in Punjab

Introduction: The incidence of diabetes in urban Punjab is on the r increasing year by year. Material and methods: This 24 week study was designed to compare vildagliptin as an add-on therapy in patients of type 2 diabetes mellitus inadequately controlled with metformin alone in Punjabi population. Sixty patients were randomized in two groups to receive either vildagliptin 100 mg (group 1) or pioglitazo primary efficacy end point was change in FBG, PPG and HbA1c. Secondary end point included lipid profile, body weight and peripheral edema. Results: There was no significant groups. There was significant decrease in mean body weight in group 1 in contrast to significant increase in group 2. Both the treatment groups reported a significant decrease in TG, TC, LDL and increase in HDL. Conclusion: Vildagliptin displays robust efficacy with the added benefits of a much lower risk of peripheral edema, hypoglycemia and no weight gain, making it a promising alternative to pioglitazone as an add-on therapy to metformin in Punjabi population 2, Issue 1, January, 2015. 1* , Rupinder Kaur 2 , Mahesh Jindal Maharaja Ganga Singh Dental College and Sriganganagar, Rajasthan, India Sunam, Punjab, India amita.jindal19@yahoo.in . Comparative study: Efficacy and -on therapy to metformin in poorly controlled . IAIM, 2015; 2(1): 83-94. www.iaimjournal. com Accepted on: ise and the number of diabetics is ne 30 mg (group 2) in addition to metformin 1000 mg. The difference between mean reduction in FBG, PPG and HbA1c in both . ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)
Review: Review of Nurse Home Visiting Interventions for Community-Dwelling Older Persons With Existing Disability

Despite there being a considerable number of meta-analyses and reviews synthesizing the nurse in-home visiting literature, there have been no reviews examining nurse in-home visiting for patients who are already disabled. This article presents a literature review and synthesis of 10 trials targeted on older adults with disability. The review is organized into structure and process components related to the outcome variable disability based on the classic Donabedian model. The review suggests that the components of in-home visiting associated with favorable disability outcomes include multiple home visits, geriatric training and experience, health provider collaboration, multidimensional assessment, and theory use. In contrast, lack of process measures, physician collaboration, training, and specific intervention components targeting disability are associated with ineffective interventions. This review helps provide insight into variables that influence disability outcomes as well as the development of best-practice models of in-home visiting to older adults with existing disability.