Miracle-dz/UniFAR-FTUs huggingface dataset:
Getting the right answers for the right reasons: Linking measurements, analyses, and models to advance the science of hydrology

The science of hydrology is on the threshold of major advances, driven by new hydrologic measurements, new methods for analyzing hydrologic data, and new approaches to modeling hydrologic systems. Here I suggest several promising directions forward, including (1) designing new data networks, field observations, and field experiments, with explicit recognition of the spatial and temporal heterogeneity of hydrologic processes, (2) replacing linear, additive “black box” models with “gray box” approaches that better capture the nonlinear and non‐additive character of hydrologic systems, (3) developing physically based governing equations for hydrologic behavior at the catchment or hillslope scale, recognizing that they may look different from the equations that describe the small‐scale physics, (4) developing models that are minimally parameterized and therefore stand some chance of failing the tests that they are subjected to, and (5) developing ways to test models more comprehensively and incisively. I argue that scientific progress will mostly be achieved through the collision of theory and data, rather than through increasingly elaborate and parameter‐rich models that may succeed as mathematical marionettes, dancing to match the calibration data even if their underlying premises are unrealistic. Thus advancing the science of hydrology will require not only developing theories that get the right answers but also testing whether they get the right answers for the right reasons.
Bioassay and relative cytotoxic potency of cyclophosphamide metabolites generated in vitro and in vivo.

Summary Cytotoxic potencies of cyclophosphamide, 4-ketocyclophosphamide, carboxyphosphamide, mechlorethamine (HN2), bis(2-chloroethyl)amine (nor-HN2), chlorambucil, acrolein, and cyclophosphamide metabolites generated in vivo and in vitro were determined via bioassay. Our bioassay procedure was to incubate the potential cytotoxic agent with Walker 256 ascites cells in vitro , inject these cells into host rats, record survival times, estimate the number of viable cells which must have been injected to account for the observed survival time, and calculate percentage cell kill from these estimates. A log-linear relationship between tumor cell kill and exposure time or drug concentration was observed. Cyclophosphamide and 4-ketocyclophosphamide were noncytotoxic, and incubation of the latter with a microsomal or 105,000 × g supernatant fraction did not activate it. Acrolein and carboxyphosphamide were only minimally cytotoxic. HN2, chlorambucil, and nor-HN2 all were cytotoxic; HN2 was most and nor-HN2 was least potent. The cytotoxic potency of cyclophosphamide metabolites generated in vitro and in vivo was expressed as the concentration of metabolite(s) in nor-HN2 or formaldehyde equivalents that was required to kill 90% of the tumor cells. For total cyclophosphamide metabolites obtained after the incubation of cyclophosphamide with hepatic microsomes or with a 9000 × g supernatant fraction and from blood or urine after cyclophosphamide injection, the concentrations of drug required to kill 90% of the tumor cells were 0.087, 0.42, 0.66, and 4.5 µm, respectively, when expressed in nor-HN2 equivalents, and were 0.035, 0.037, 0.041, and 0.17 µm, respectively, when expressed in formaldehyde equivalents. Cyclophosphamide, 4-ketocyclophosphamide, carboxyphosphamide, nor-HN2, and acrolein could not account for the cytotoxic activity of the cyclophosphamide metabolite generated in vitro by hepatic microsomal mixedfunction oxidase action, since the latter was a more potent cytotoxic agent than any of these compounds, although it was less potent than HN2. Trapping of the microsome-generated metabolite with semicarbazide reduced its cytotoxic potency. These data support the contention that cyclophosphamide is activated (to a cytotoxic metabolite) primarily by mixed-function oxidase action of the hepatic endoplasmic reticulum which oxidizes it to aldophosphamide, and that aldophosphamide is inactivated (as a cytotoxic agent) by aldehyde oxidase (EC 1.2.3.1) and/or aldehyde dehydrogenase (EC 1.2.1.3), which oxidize(s) aldophosphamide to carboxyphosphamide. In addition, the data provide estimates of the potency of aldophosphamide as a cytotoxic agent relative to that of other alkylating agents.
Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients.

Chronic metabolic acidosis (CMA) in human beings is characterized by increased renin-angiotensin-aldosterone (RAA) activity and cortisol secretion as well as nitrogen wasting. The purpose of this study was to examine whether and to what extent increased RAA activity (i.e., angiotensin II or aldosterone) regulates acid-base equilibrium in CMA and thus might co-determine the severity of acidosis. CMA was induced in 8 normal subjects by oral NH4Cl administration (2.1 mmol/kg body weight per day) for 7 days, followed by a 7-day period of spironolactone (100 mg, 4 times a day by mouth), followed by a 4-day period of spironolactone and losartan (100 mg, every day by mouth). NH4Cl feeding was continued during all study periods. Spironolactone resulted in exacerbation of acidosis ((HCO3)p decreased from 19.8+/-0.4 mmol/L to 17.7+/-0.6 mmol/L, P<. 005) because of a large increase in endogenous acid production, as evidenced by significant increases in net acid excretion (116 to 185 mmol/day, P<.005), urinary anion gap (+31 mEq/day, P<.05), and sulfate excretion (+32 mEq/day, P<.05). Plasma potassium increased from 4.2 to 4.6 mmol/L (P<.05) because of decreased urinary potassium excretion (from 108 to 92 mmol/day, P<.05). Plasma angiotensin II, cortisol, aldosterone, urinary aldosterone, urinary tetrahydrocortisol, free cortisol, and nitrogen excretion increased significantly. The subsequent addition of losartan to spironolactone administration resulted in further exacerbation of acidosis ((HCO3)p decreased to 15.7+/-0.4 mmol/L, P<. 05) and hyperkalemia (5.0 mmol/L, P<.05) with no change in plasma anion gap. Renal potassium excretion decreased from 92 to 73 mmol/day (P<.05) on day 1. Exacerbation of acidosis was accounted for by a renal mechanism, as evidenced by the significant decrease in net acid excretion and unchanged urinary unmeasured anion and nitrogen excretion. We conclude the following: (1) AT-1 blockade by losartan exacerbates acidosis by inducing a distal-tubular acidification defect. Angiotensin II is an important modulator of the renal acid excretory response to CMA in human beings. (2) Inhibition of aldosterone action by spironolactone in CMA results in an increase in endogenous acid production and exacerbates acidosis by a non-renal mechanism that is mediated, at least in part, by exacerbated hyperglucocorticoidism.
Induction of LTP in the human auditory cortex by sensory stimulation

High‐frequency, repetitive, auditory stimulation was used to determine whether induction of a long‐lasting increase of the human auditory evoked potential (AEP) was possible. Recording non‐invasively with electroencephalogram scalp electrodes, stable increases in amplitude were observed in the N1 component of the AEP, which is thought to reflect activity within auditory cortex (N1). The increase was maintained over an hour and was shown to be independent of alterations in the state of arousal. This is the first demonstration of the induction of long‐lasting plastic changes in AEPs, and suggest that this represents the first direct demonstration of long‐term potentiation in the auditory cortex of normal, intact humans.
A model-driven approach to warp/thread-block level GPU cache bypassing

The high amount of memory requests from massive threads may easily cause cache contention and cache-miss-related resource congestion on GPUs. This paper proposes a simple yet effective performance model to estimate the impact of cache contention and resource congestion as a function of the number of warps/thread blocks (TBs) to bypass the cache. Then we design a hardware-based dynamic warp/thread-block level GPU cache bypassing scheme, which achieves 1.68x speedup on average on a set of memory-intensive benchmarks over the baseline. Compared to prior works, our scheme achieves 21.6% performance improvement over SWL-best [29] and 11.9% over CBWT-best [4] on average.
Modulation of Adipogenic Conditions for Prospective Use of hADSCs in Adipose Tissue Engineering

Modern strategies in adipose tissue engineering (ATE) take advantage of the easy harvest, abundance and differentiation potential towards mesenchymal lineages of hADSCs. The controlled conversion of hADSCs to committed adipogenic precursors and further mature adipocytes formation is important for good long-term results in soft tissue regeneration. Thus, in this study, we report: (i) the isolation of the processed lipoaspirate (PLA) cells from adipose tissue and sanguine fractions; (ii) the phenotypic characterization of the PLA descendants; (iii) the design of a novel protocol for the modulation of adipogenic conditions in the perspectives of ATE applications. To modulate the differentiation rate through our protocol, we propose to selectively modify the formulation of the adipogenic media in accordance with the evolution of the process. Therefore, we aimed to ensure the long-term proliferation of the precursor cells and to delay the late adipogenic events. The status of differentiation was characterized in terms of intracellular lipid accumulation and reorganization of the cytoskeleton simultaneously with perilipin protein expression. Moreover, we studied the sequential activation of PPARγ2, FAS, aP2 and perilipin genes which influence the kinetics of the adipogenic process. The strategies developed in this work are the prerequisites for prospective 3D regenerative systems.
Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication

Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called “zygomycetes,” R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99–880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin–proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14α-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments.
Stochastic inflation revisited: non-slow-roll statistics and DBI inflation

Stochastic inflation describes the global structure of the inflationary universe by modeling the super-Hubble dynamics as a system of matter fields coupled to gravity where the sub-Hubble field fluctuations induce a stochastic force into the equations of motion. The super-Hubble dynamics are ultralocal, allowing us to neglect spatial derivatives and treat each Hubble patch as a separate universe. This provides a natural framework in which to discuss probabilities on the space of solutions and initial conditions. In this paper we derive an evolution equation for this probability for an arbitrary class of matter systems, including DBI and k-inflationary models, and discover equilibrium solutions that satisfy detailed balance. Our results are more general than those derived assuming slow roll or a quasi-de Sitter geometry, and so are directly applicable to models that do not satisfy the usual slow-roll conditions. We discuss in general terms the conditions for eternal inflation to set in, and we give explicit numerical solutions of highly stochastic, quasi-stationary trajectories in the relativistic DBI regime. Finally, we show that the probability for stochastic/thermal tunneling can be significantly enhanced relative to the Hawking–Moss instanton result due to relativistic DBI effects.
Rehydration characteristics of dehydrated West African pepper (Piper guineense) leaves

The rehydration characteristics of dehydrated West African pepper leaves were investigated at hydration temperatures of 28, 60, 70, and 80°C. Four treatments were given to the leaves: blanched and sun dried, unblanched and sun dried, blanched and shade dried, and unblanched and shade dried. The hydration process of the dehydrated leaves was adequately described by the Peleg's equation. As the hydration temperature increased from 28 to 70°C, there was a significant decrease in the Peleg's constant K1, while for most of the leaves the Peleg's constant K2 varied with temperature. Rehydration ratio values ranged from 3.75 in blanched shade dried leaves to 4.26 in unblanched sun dried leaves with the unblanched leaves generally exhibiting higher ratios than the blanched leaves.
PKCζ regulates cell polarisation and proliferation restriction during mammary acinus formation

Mammary epithelial cells organize in three dimensions and generate acini when supported on laminin-rich extracellular matrix. Acinus formation begins with the apicobasal polarisation of the outer cells of the assembly and the withdrawal of these cells from the cell cycle. Internal cells then clear out to form a hollow lumen. Here, we show that PKCζ is phosphorylated (at T410) and activated in the early stages of acinus formation in both primary cells and MCF10A cells, and during mammary tree maturation in vivo. Phospho-PKCζ colocalised with tight junction components and bound to the Par polarising complex in developing acini. To further investigate the importance of PKCζ phosphorylation in this context, acinus formation was studied in MCF10A cells overexpressing non-phosphorylatable (T410A) or ‘constitutively phosphorylated’ (T410E) PKCζ. In both cell types, acinus-associated cell polarisation and lumen clearance were compromised, emphasising the importance of regulated phosphorylation of PKCζ at T410 for successful acinus formation. PKCζ can be activated in a phosphorylation (at T410)-dependent and a phosphorylation-independent manner. Cells overexpressing a complete kinase-deficient PKCζ (K281W) displayed a cell polarising deficit, but also generated large ‘multi-acinar’ structures with associated early lumenal cell hyperproliferation. Therefore our data shows, for the first time, that two separable PKCζ activities (one phosphorylation-dependent, the other not) are required to support the cell polarisation and proliferation restriction that underpins successful acinus formation. Paralleling these contributions, we found that low levels of PKCζ mRNA expression are associated with more ‘poorly differentiated’ tumours and a poor outcome in a cohort of 295 breast cancer patients.
Method for Providing Electrovibration with Uniform Intensity

Electrovibration is a type of surface haptics that can modulate lateral forces acting between a fingertip and a touch surface. Electrovibration is fast, consumes little power, and does not involve the use of any mechanical actuators. However, it suffers from problems such as nonuniform perceived intensity due to varying environmental impedances, as well as possible electric shock, which have to be solved for commercialization. In this paper, a current feedback method is proposed to provide uniform intensity of electrovibration, regardless of the varying environmental impedances. The proposed method can also prevent electric shock. To show the effectiveness of the proposed method, a hardware prototype was developed and a user study was conducted. The user study result shows that the proposed current control method can provide significantly more uniform perceived intensity of electrovibration as compared with the conventional voltage control method.
The Evolving Role of Molecular Markers in the Diagnosis and Management of Diffuse Glioma

While the classification of diffuse gliomas has relied on the examination of morphologic features supplemented with techniques such as immunohistochemistry, there is an increasing recognition of substantial biologic diversity within morphologically defined entities. High-throughput technologies, in particular studies that integrate genome-wide data from diverse molecular platforms, increasingly identify the existence of robust and distinct glioma subtypes. While treatment advances and improvement of outcomes for patients with diffuse glioma have been modest, there may be benefit to integrate findings from biologic studies into clinical practice to enhance the precision of treatment for these diseases. Recent examples such as the identification of mutations in IDH1 and IDH2 as an early genetic event that is predominantly in lower-grade gliomas (grades 2 and 3) underscore the importance of molecular discovery leading to the ability to develop subclassifications with prognostic and potentially therapeutic implications. In contrast, glioblastoma (grade 4), the most common and aggressive glioma, typically arises without IDH mutation, supporting the need for different therapeutic approaches. Additional genomic and epigenomic signatures are generally nonoverlapping between IDH-mutant and IDH wild-type diffuse glioma, and despite comparable histopathology, IDH-mutant gliomas can be considered as biologically distinct from IDH wild-type gliomas. In this CCR Focus article, we highlight and summarize the current understanding of recent molecular findings and the relationships of these findings to clinical trials and clinical management. See all articles in this CCR Focus section, “Discoveries, Challenges, and Progress in Primary Brain Tumors. ” Clin Cancer Res; 20(22); 5601–11. ©2014 AACR.
Minimizing Manual Annotation Cost in Supervised Training from Corpora

Corpus-based methods for natural language processing often use supervised training, requiring expensive manual annotation of training corpora. This paper investigates methods for reducing annotation cost by sample selection. In this approach, during training the learning program examines many unlabeled examples and selects for labeling (annotation) only those that are most informative at each stage. This avoids redundantly annotating examples that contribute little new information. This paper extends our previous work on committee-based sample selection for probabilistic classifiers. We describe a family of methods for committee-based sample selection, and report experimental results for the task of stochastic part-of-speech tagging. We find that all variants achieve a significant reduction in annotation cost, though their computational efficiency differs. In particular, the simplest method, which has no parameters to tune, gives excellent results. We also show that sample selection yields a significant reduction in the size of the model used by the tagger.
The economic burden of caregiving on families of children and adolescents with cancer: A population‐based assessment

Childhood cancer represents a relevant economic burden on families. The preferred tool to investigate family expenditure is the retrospective questionnaire, which is subject to recall errors and selection bias. Therefore, in the present study the economic burden of caregiving on families of children and adolescents (0–19 years of age) with cancer was analysed using administrative data as an alternative to retrospective questionnaires.
Influence of moderate chronic wine consumption on insulin sensitivity and other correlates of syndrome X in moderately obese women.

Epidemiologic studies indicate that alcohol consumption is associated with improved insulin sensitivity; however, scant experimental evidence confirms this observation. To determine the effects of regular moderate wine consumption on insulin sensitivity, 20 overweight women (body mass index [BMI], 29.8 +/- 2.2 kg/m2) participated in a 20-week free-living randomized crossover trial. The subjects, serving as their own controls, consumed wine (190 mL red wine, 13% vol/vol ethanol, 5 days per week) for 10 weeks and abstained for 10 weeks or vice versa. The dependent variables (body weight, BMI, percent body fat, blood pressure, fasting blood glucose and insulin, blood lipids, dietary intake, and insulin sensitivity by intravenous glucose tolerance test [IVGTT]) were measured at the pretest, at the 10-week crossover, and at the 20-week completion of the study. Data were analyzed at the pretest and at completion of the wine drinking and abstention periods of the study using ANOVA by order of treatment. Fasting glucose remained unchanged (mean +/- SD; P > .05) throughout the experiment (pretest, drinking, and abstention, 91.1 +/- 9.2, 91.6 +/- 9.1, and 88.5 +/- 11.2 mg/dL), as did the measures of insulin sensitivity, fasting insulin (pretest, drinking, and abstention, 8.6 +/- 3.3, 8.6 +/- 4.1, and 9.1 +/- 4.7 microU/mg) and the insulin sensitivity index (3.60 +/- 2.96, 3.25 +/- 2.17, and 3.30 +/- 1.84). Body composition and blood lipids also remained unchanged (P > .05) during treatment. Moderate wine consumption at this dose in overweight women did not improve or impair insulin sensitivity, nor did it change any of the known correlates of insulin sensitivity, including body weight and composition, blood lipids, and blood pressure.