Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I and Pharmacokinetic Study of the Cytotoxic Ether Lipid Ilmofosine Administered by Weekly Two-Hour Infusion in Patients with Advanced Solid Tumors

Purpose: A Phase I trial was performed to determine the dose-limiting toxicity and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl-lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in patients with solid tumors. Experimental Design: Thirty-nine patients were entered into a trial of ilmofosine administered weekly for 4 weeks followed by a 2-week rest period. Dose escalation occurred in 10 levels from 12 to 650 mg/m2. Results: Thirty-six patients were evaluable for toxicity. The median number of cycles per patient was 1 (range, 1–4). Dose-limiting gastrointestinal toxicity occurred at 650 mg/m2 with grade 3 nausea in two patients and grade 3 vomiting and diarrhea in one patient. Grade 2 diarrhea was observed in four of six patients treated at 550 mg/m2. In addition, two patients treated at 550 mg/m2 and two patients treated at 650 mg/m2 experienced a decline in performance status of two or more levels that was determined to be due to treatment. There were no tumor responses. Stabilization of disease for at least 8 weeks occurred in six patients. Plasma concentrations of ilmofosine and its sulfoxide metabolite were evaluated by high-pressure liquid chromatography. The elimination of both compounds was biexponential with terminal half-lives of ∼40 h for ilmofosine and 48 h for the sulfoxide. The area under the concentration-time curve was dose-proportional for each compound, and there was no evidence of saturable kinetics. Conclusions: The dose-limiting toxicity of ilmofosine is gastrointestinal and the recommended dose for Phase II trials is 450 mg/m2 as a 2-h weekly infusion. The relatively long half-life of ilmofosine and its active metabolite support the use of this intermittent schedule.
In silico Analysis of Combinatorial microRNA Activity Reveals Target Genes and Pathways Associated with Breast Cancer Metastasis

Abstract Aberrant microRNA activity has been reported in many diseases, and studies often find numerous microRNAs concurrently dysregulated. Most target genes have binding sites for multiple microRNAs, and mounting evidence indicates that it is important to consider their combinatorial effect on target gene repression. A recent study associated the coincident loss of expression of six microRNAs with metastatic potential in breast cancer. Here, we used a new computational method, miR-AT! , to investigate combinatorial activity among this group of microRNAs. We found that the set of transcripts having multiple target sites for these microRNAs was significantly enriched with genes involved in cellular processes commonly perturbed in metastatic tumors: cell cycle regulation, cytoskeleton organization, and cell adhesion. Network analysis revealed numerous target genes upstream of cyclin D1 and c-Myc, indicating that the collective loss of the six microRNAs may have a focal effect on these two key regulatory nodes. A number of genes previously implicated in cancer metastasis are among the predicted combinatorial targets, including TGFB1, ARPC3, and RANKL. In summary, our analysis reveals extensive combinatorial interactions that have notable implications for their potential role in breast cancer metastasis and in therapeutic development.
Re-Examination of Louis Pasteur’s S-Shaped Flask Experiment

neither negative control nor control to prevent microbes from escaping was set when the S-shaped flask experiments were performed by Pasteur. Microscope was not used to observe the media in the flasks. Louis Pasteur’s S-shaped flask experiment was re-examined by using U-shaped flasks, modified S-shaped flasks and microscope. A mixture of microbes was isolated from the room air, from which one rod-shaped Bacillus species with proposed name Bacillus gaso-mobilis sp nov and one grape-shaped Staphylococcus species with proposed name of Staphylococcus gaso-mobilis sp nov were identified. Their penicillin and ampicillin resistant strains containing plasmids were isolated. These bacteria could change color, produce odor and automatically move in the air. They did not form colonies on solid media. They had a high suspension capacity in liquid media. Their light absorbance peaked at the wave length of 320nm. It was concluded that there were flaws with Louis Pasteur’s S-shaped flask experiments. Keywords—Bacteria, gaso-mobile, re-examine, S-shaped flasks.
Factor structure of a Cantonese-version Pittsburgh Sleep Quality Index

The objectives of this study were to translate, validate and test the factor structure of a Cantonese version of the Pittsburgh Sleep Quality Index (Cantonese-PSQI) in support of its use among Cantonese-speaking Chinese in Hong Kong, southern China and Chinese immigrant communities in the West. The study involved Cantonese-speaking Chinese aged 45 or over in Hong Kong. A cross-sectional survey of 97 participants was firstly conducted to validate the Cantonese-PSQI. A second survey of 794 participants identified the best-fitted factor structure of the scale. Confirmatory factor analysis then functioned to develop and test a single-factor model, a two-factor model, and a three-factor model. The one-factor model turned out to be unacceptable due to its poor fit (L2 = 303.408, d.f. = 14, SRMR = 0.085; RMSEA = 0.161; CFI = 0.805). The three-factor model, despite its very good fit (L2 = 36.450, d.f. = 11, SRMR = 0.022; RMSEA = 0.054; CFI = 0.983), was unacceptable because of the extraordinarily high correlation (r = 0.928) between two of its three factors, namely the sleep quality factor and the daily disturbances factor. The two-factor model showed a good fit with the data of all the participants (L2 = 46.339, d.f. = 13, SRMR = 0.028; RMSEA = 0.057; CFI = 0.978), and with those of the middle-aged, the young-old and the old-old groups. The two-factor model of the Cantonese-PSQI characterized by sleep efficiency and sleep quality is therefore better than the original one-factor model and the three-factor model for measuring the sleep quality of middle-aged and older Cantonese-speaking Chinese.
Cost-Effectiveness of Hub-and-Spoke Telestroke Networks for the Management of Acute Ischemic Stroke From the Hospitals’ Perspectives

Background— A hub-and-spoke telestroke network is an effective way to extend quality acute stroke care to remote hospitals and to improve patient outcomes. This study assessed the cost-effectiveness of a telestroke network in the management of acute ischemic stroke from the perspectives of a network, a hub hospital, and a spoke hospital. Methods and Results— A model was developed to compare costs and effectiveness with and without a telestroke network over a 5-year time horizon. The model considered differences in rates of teleconsultations, intravenous thrombolysis, endovascular stroke therapies, and spoke-to-hub transfers. These inputs were estimated through the use of data from Georgia Health Sciences University and Mayo Clinic telestroke networks. A network model with 1 hub and 7 spokes predicted that 45 more patients would be treated with intravenous thrombolysis and 20 more with endovascular stroke therapies per year compared with no network, leading to an estimate of 6.11 more home discharges. Each year, a telestroke network was associated with $358 435 in cost savings; each spoke had $109 080 in cost savings, whereas the hub had positive costs of $405 121. However, cost sharing can be arranged so that each hospital could achieve an equal amount of cost savings ($44 804/y). Results were sensitive to the number of spokes, marginal treatment costs in spokes and rates of transfer, and endovascular stroke therapies. Conclusions— The results of this study suggest that a telestroke network may increase the number of patients discharged home and reduce the costs borne by the network hospitals. Hospitals should consider their available resources and the network features when deciding whether to join or set up a network.
Butterfly gyroid nanostructures as a time-frozen glimpse of intracellular membrane development

High-resolution microscopy of hierarchically organized solid gyroid nanostructures sheds light on the underlying dynamic formation process. The formation of the biophotonic gyroid material in butterfly wing scales is an exceptional feat of evolutionary engineering of functional nanostructures. It is hypothesized that this nanostructure forms by chitin polymerization inside a convoluted membrane of corresponding shape in the endoplasmic reticulum. However, this dynamic formation process, including whether membrane folding and chitin expression are simultaneous or sequential processes, cannot yet be elucidated by in vivo imaging. We report an unusual hierarchical ultrastructure in the butterfly Thecla opisena that, as a solid material, allows high-resolution three-dimensional microscopy. Rather than the conventional polycrystalline space-filling arrangement, a gyroid occurs in isolated facetted crystallites with a pronounced size gradient. When interpreted as a sequence of time-frozen snapshots of the morphogenesis, this arrangement provides insight into the formation mechanisms of the nanoporous gyroid material as well as of the intracellular organelle membrane that acts as the template.
Dynamic Systems and the Challenge of Sustainability

Dynamism, uncertainty and complexity dominate today’s world. Yet many policy interventions ignore this, and so often fail. What is missing is a rigorous and systematic approach to addressing dynamics, one that encompasses an understanding of complex system dynamics and provides a useable guide to action. This paper is a first attempt by the STEPS Centre to address this challenge. To open, the paper reviews a range of different approaches to understanding dynamics, including complexity science, dynamic ecology, industrial socio-technical systems and policy and organisational responses, exploring opportunities, complementarities and gaps. Next, the paper examines how such approaches to understanding dynamic systems can illuminate and extend approaches to sustainable development, concluding that a new science for sustainability requires an integration of now well-elaborated non-equilibrium perspectives from the natural sciences with constructivist social science perspectives. Drawing on these diverse literatures and debates, the final section presents a heuristic framework for addressing dynamic contexts in debates about sustainable development. In conclusion, the paper highlights three things: the need to address diverse framings of both system structure and function, the need to assess trade-offs between system properties that underlie attempts to achieve sustainability and the need to be continuously reflexive about the diverse options implied.
Effects of daytime melatonin infusion in young adults.

Daytime oral melatonin typically exerts soporific and thermoregulatory effects; however, it is not clear whether these effects reflect the normal physiological response to endogenous nocturnal melatonin production. We infused melatonin at doses that produced physiological and supraphysiological steady-state levels in 24 young adults during two daytime bed rest protocols. From 1000 to 1630, subjects were infused intravenously with saline or melatonin in counterbalanced order. Each group of eight subjects received melatonin (and saline) infusions at one dose rate: 0.04 microg . h-1 . kg body wt-1 (low), 0.08 microg . h-1 . kg-1 (medium), or 8.0 microg . h-1 . kg-1 (high). Low and medium melatonin infusions produced plasma and saliva levels within the normal nocturnal range observed in young adults. These levels were not associated with any changes in rectal, hand, forehead, or tympanic temperatures or with subjective sleepiness. High melatonin produced supraphysiological plasma and saliva levels and was associated with a significant attenuation in the daytime increase in rectal temperature, significantly increased hand temperature, and greater sleepiness. It is not yet clear whether the thermoregulatory and soporific effects of daytime supraphysiological melatonin administration are equivalent to the physiological responses to endogenous melatonin.
Integration of a virus membrane protein intothe lipid bilayer of target cells as a prerequisite for immune cytolysis. Specific cytolysis after virosome- target cell fusion

Structural requirements for membrane antigens on target cells to mediate immune cytolysis were studied in a model system with purified membrane proteins from Semliki Forest virus (SFV). These SFV spike proteins were isolated in the form of detergent- and lipid-free protein micelles (29S complexes) or, after reconstitution into lipid vesicles, in the form of virosomes. Both the 29S complexes and the virosomes were found to bind well to murine tumor cells (P815 or Eb). When these cells, however, were used as target cells in complement-dependent lysis or in antibody-dependent cell- mediated cytotoxicity assays in the presence of anti-SFV serum, they were not lysed, although they effectively bound the antibody and consumed complement. The same tumor cells infected with SFV served as positive controls in both assays. Different results were obtained when inactivated Sendai virus was added as a fusion reagent to the cells coated with either virosomes or 29S complexes. Under these conditions the virosome-coated cells became susceptible to SFV- specific lysis, whereas the 29S complex-coated cells remained resistant. Evidence that the susceptibility to lysis ofvirosome-coated cells was dependent on active fusion and, therefore, integration of the viral antigens into the lipid bilayer of the target cells was derived from control experiments with enzyme-treated Sendai virus preparations. The 29S complexes and the virosomes partially and selectively blocked the target cell lysis by anti-H-2 sera but not by anti-non-H-2 sera confirming our previous finding that major histocompatibility antigens serve as receptors for SFV. The general significance of these findings for mechanisms of immune cytolysis is dicussed.
Coating and Surface Treatments on Orthodontic Metallic Materials

Metallic biomaterials have been extensively used in orthodontics throughout history. Gold, stainless steel, cobalt-chromium alloys, titanium and its alloys, among other metallic biomaterials, have been part of the orthodontic armamentarium since the twentieth century. Metals and alloys possess outstanding properties and offer numerous possibilities for the fabrication of orthodontic devices such as brackets, wires, bands, ligatures, among others. However, these materials have drawbacks that can present problems for the orthodontist. Poor friction control, allergic reactions, and metal ionic release are some of the most common disadvantages found when using metallic alloys for manufacturing orthodontic appliances. In order to overcome such weaknesses, research has been conducted aiming at different approaches, such as coatings and surface treatments, which have been developed to render these materials more suitable for orthodontic applications. The purpose of this paper is to provide an overview of the coating and surface treatment methods performed on metallic biomaterials used in orthodontics.
Delay-constrained area recovery via layout-driven buffer optimization

During logic optimization/mapping, a designer or a synthesis tool constructs buffer trees to improve the delay characteristics of the circuit. However, since wire delays and capacitances are not known, the timing information is inherently inaccurate at this stage. After cells have been placed and nets routed, wire loads and delays are known more accurately. It is possible then that buffer trees generated earlier can be improved, resulting in better delay and area for the design. Large, industrial digital designs can have as many as 30% cells that are buffers. Optimizing (deleting and/or replacing) buffers can lead to significant area and/or delay reduction. In this paper, we address the problem of recovering maximum possible area of a mapped, approximately placed and globally routed digital design via buffer optimization without degrading the circuit timing or overloading the cell pins. We propose an exact, layout-driven algorithm to minimize the area of an extended net without increasing the circuit delay, for both buffer deletion and buffer insertion/deletion. Our key algorithmic contribution is to organize all possible buffer insertion/deletion choices with identical area components in a sorted array and to exploit that in devising efficient solution combining, merging, and pruning techniques. We propose and compare various, schemes for applying the single-net algorithm to an entire design. The most formidable challenge is to handle large designs in a reasonable time under the memory constraint. On average, 50.8% of the buffer area of already optimized, real industrial designs could be reclaimed without degrading the circuit delay or overloading any cell pins.
Large scale data mining to improve usability of data - an intelligent archive testbed

-Research in certain scientific disciplines-including Earth science, particle physics, and astrophysics-continually faces the challenge that the volume of data needed to perform valid scientific research can at times overwhelm even a sizable research community. The desire to improve utilization of this data gave rise to the Intelligent Archives project, which seeks to make data archives active participants in a knowledge building system capable of discovering events or patterns that represent new information or knowledge. Data mining can automatically discover patterns and events, but it is generally viewed as unsuited for large-scale use in disciplines like Earth science that routinely involve very high data volumes. Dozens of research projects have shown promising uses of data mining in Earth science, but all of these are based on experiments with data subsets of a few gigabytes or less, rather than the tera-bytes or petabytes typically encountered in operational systems. To bridge this gap, the Intelligent Archives project is establishing a testbed with the goal of demonstrating the use of data mining techniques in an operationally-relevant environment. This paper discusses the goals of the testbed and the design choices surrounding critical issues that arose during testbed implementation.
Chs7p, a New Protein Involved in the Control of Protein Export from the Endoplasmic Reticulum that Is Specifically Engaged in the Regulation of Chitin Synthesis in Saccharomyces cerevisiae

The Saccharomyces cerevisiae CHS7 gene encodes an integral membrane protein located in the ER which is directly involved in chitin synthesis through the regulation of chitin synthase III (CSIII) activity. In the absence of CHS7 product, Chs3p, but not other secreted proteins, is retained in the ER, leading to a severe defect in CSIII activity and consequently, to a reduced rate of chitin synthesis. In addition, chs7 null mutants show the yeast phenotypes associated with a lack of chitin: reduced mating efficiency and lack of the chitosan ascospore layer, clear indications of Chs7p function throughout the S. cerevisiae biological cycle. CHS3 overexpression does not lead to increased levels of CSIII because the Chs3p excess is retained in the ER. However, joint overexpression of CHS3 and CHS7 increases the export of Chs3p from the ER and this is accompanied by a concomitant increase in CSIII activity, indicating that the amount of Chs7p is a limiting factor for CSIII activity. Accordingly, CHS7 transcription is increased when elevated amounts of chitin synthesis are detected. These results show that Chs7p forms part of a new mechanism specifically involved in Chs3p export from the ER and consequently, in the regulation of CSIII activity.
LTCC based microfluidic optical detector

A new fiber-based optical microfluidic detector was designed for low-volume sample measurement. Microdetector was fabricated by use of LTCC (low temperature co-fired ceramic) technology. The microdevice was made as separate module, which can be connected via tubing to any microanalytical system. The designed detector allowed to measure an optical absorbance (transmittance) in the analytical channel. Presented microfluidic detector can be also applied as a part of integrated muTAS (micro-total analysis system). The preliminary tests indicate linear absorbance detection in the range 9.5-28.5 mug/ml of cochineal red A and 10-20 mug/ml of sunset yellow in the test solutions
Internal consistency of the CHAMPS physical activity questionnaire for Spanish speaking older adults.

INTRODUCTION The Community Healthy Activities Model Program for Seniors (CHAMPS) is a physical activity monitoring questionnaire for people between 65 to 90 years old. This questionnaire has been previously translated to Spanish to be used in the Latin American population. PURPOSE To adapt the Spanish version of the CHAMPS questionnaire to Puerto Rico and assess its internal consistency. METHODS An external review committee adapted the existent Spanish version of the CHAMPS to be used in the Puerto Rican population. Three older adults participated in a second phase with the purpose of training the research team. After the second phase, 35 older adults participated in a third content adaptation phase. During the third phase, the preliminary Spanish version for Puerto Rico of the CHAMPS was given to the 35 participants to assess for clarity, vocabulary and understandability. Interviews to each participant in the third phase were carried out to obtain feedback and create a final Spanish version of the CHAMPS for Puerto Rico. After analyses of this phase, the external review committee prepared a final Spanish version of the CHAMPS for Puerto Rico. The final version was administered to 15 older adults (76 +/- 6.5 years) to assess the internal consistency by using Cronbach's Alpha analysis. RESULTS The questionnaire showed a strong internal consistency of 0.76. The total time to answer the questionnaire was 17.4 minutes. CONCLUSION The Spanish version of the CHAMPS questionnaire for Puerto Rico suggested being an easy to administer and consistent measurement tool to assess physical activity in older adults.
On‐line coupling of size‐exclusion chromatography and capillary zone electrophoresis via a reversed‐phase C18 trapping column for the determination of peptides in biological samples

Since biologically active peptides usually exhibit their effects in low concentrations, the development of sensitive analytical methods has become a challenge. In this paper, a multidimensional system is presented, consisting of a size‐exclusion chromatographic (SEC) separation followed by a trapping procedure on a 4 mm×3 mm ID reversed‐phase C18 (RP18) column with subsequent elution of the trapped fraction and separation by capillary zone electrophoresis (CZE). The system has been tested with mixtures of six enkephalins and albumin, mimicking biological matrices such as plasma and cerebrospinal fluid. After separation of albumin from the enkephalins in the SEC dimension a heart‐cut of 200 μL, containing the enkephalin peak, is taken, concentrated on the RP18 microcolumn and, after elution with a 20 μL plug of 80% acetonitrile, electrokinetically injected into the CZE system, where stacking and separation is achieved. While validation shows generally good linearity and reproducibility, the quantitation limit with UV detection is acceptable (2.5 μg/ mL with an injection volume of 50 μL).