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Cyclopentenyl cytosine (CPE-C) is an investigational drug that is active against human solid tumor xenografts. The 5'-triphosphate of CPE-C inhibits CTP synthase, and depletes CTP and dCTP pools. We conducted a phase I clinical trial of CPE-C given as a 24-h continuous i.v. infusion every 3 weeks in 26 adults with solid tumors. The starting dose rate, 1 mg/m2 per h, was selected on the basis of both preclinical studies and pharmacokinetic data from two patients obtained after a test dose of 24 mg/m2 CPE-C as an i.v. bolus. Dose escalation was guided by clinical toxicity. A total of 87 cycles were given, and ten patients received four or more cycles. The mean CPE-C steady-state plasma levels (Cpss) increased linearly from 0.4 microM to 3.1 microM at dose levels ranging from 1 to 5.9 mg/m2 per h (actual body weight); the mean total body clearance was 146 +/- 38 ml/min per m2. CPE-C was eliminated by both renal excretion of intact drug and deamination to cyclopentenyl uracil in an apparent 2:1 ratio. CTP synthase activity in intact bone marrow mononuclear cells was inhibited by 58% to 100% at 22 h compared to matched pretreatment samples at all CPE-C dose levels. When all data were combined, flux through CTP synthase was decreased by 89.6% +/- 3.1% at 22 h (mean +/- SE, n = 16), and remained inhibited by 67.6% +/- 7.7% (n = 10) for at least 24 h post-CPE-C infusion. Granulocyte and platelet toxicities were dose-dependent, and dose-limiting myelosuppression occurred during the initial cycle in two of three patients treated with 5.9 mg/m2 per h. Four of 11 patients (4 of 20 cycles) who received 4.7 mg/m2 per h CPE-C experienced hypotension 24-48 h after completion of the CPE-C infusion during their first (n = 2), third (n = 1) and sixth cycles (n = 1), respectively. Two of these patients died with refractory hypotension despite aggressive hydration and cardiopulmonary resuscitation. One of 12 patients (28 total cycles) treated with 3.5 mg/m2 per h CPE-C experienced orthostatic hypotension during cycle 1, and this patient had a second episode of orthostatic hypotension at a lower dose (3.0 mg/m2 per h). Hypotension was not seen in patients receiving < or = 2.5 mg/m2 per h CPE-C.(ABSTRACT TRUNCATED AT 400 WORDS)

Person-Job Fit is the process of matching the right talent for the right job by identifying talent competencies that are required for the job. While many qualitative efforts have been made in related fields, it still lacks quantitative ways of measuring talent competencies as well as the job’s talent requirements. To this end, in this article, we propose a novel end-to-end data-driven model based on a Convolutional Neural Network (CNN), namely, the Person-Job Fit Neural Network (PJFNN), for matching a talent qualification to the requirements of a job. To be specific, PJFNN is a bipartite neural network that can effectively learn the joint representation of Person-Job fitness from historical job applications. In particular, due to the design of a hierarchical representation structure, PJFNN can not only estimate whether a candidate fits a job but also identify which specific requirement items in the job posting are satisfied by the candidate by measuring the distances between corresponding latent representations. Finally, the extensive experiments on a large-scale real-world dataset clearly validate the performance of PJFNN in terms of Person-Job Fit prediction. Also, we provide effective data visualization to show some job and talent benchmark insights obtained by PJFNN.

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been coupled to in vivo microdialysis for on-line monitoring of melatonin in a freely moving rat for a period of 15 hours. A microdialysis probe was surgically implanted into the jugular vein of the rat, and deionized water was used as the perfusion medium at a flow rate of 1.0 microL/min. Microdialysis samples were collected in an on-line injector with sample injection every 30 minutes. Melatonin was dosed by intraperitoneal (i.p.) injection and then monitored by microdialysis/LC/MS/MS. The whole experiment, including the microdialysis sampling and sample injection into the LC/MS system, was fully automated. Metabolites of melatonin were identified off-line by LC/MSn experiments. Two metabolites were identified as 6-hydroxymelatonin and cyclic 2-hydroxymelatonin, consistent with ones found previously in the literature.

Questions What are the primary types of intraspecific distribution patterns and interspecific associations of tree species in the temperate–subtropical transition region? Can potential ecological mechanisms such as habitat heterogeneity, dispersal limitation, density dependence, spatial segregation, and competition between species regulate these patterns? Location The Qinling Mountains, north‐central China. Methods Ripley's K‐function, D‐function and pair correlation function were applied to assess the spatial distribution of 15 dominant tree species in a fully mapped 25‐ha plot. Complete spatial randomness (CSR), heterogeneous Poisson (HP) and random‐labelling (RL) null models were used to reveal the potential process of community construction. Results (a) Thirteen of 15 adult tree species displayed an aggregation distribution at various scales. (b) Eleven adult species (73.3%) showed significant aggregation, especially at small distances, after removing the effect of habitat. (c) The percentage of species showing additional aggregation relative to adults decreased from saplings to juveniles. The maximum strength of density dependence was negative with species abundance. (d) Only 29 (13.8%) of the species pairs showed significant small‐scale interactions. Most of the significant small‐scale associations did not occur in abundant species pairs. (e) Negative interactions of interspecific associations were more prevalent than positive ones, yet there was no consistency of the characteristics among species pairs. Conclusions Habitat heterogeneity and dispersal limitation likely contribute to the spatial pattern of tree species at different life stages. Density dependence remains the important factor in maintaining species diversity in this forest stand. Moreover, spatial segregation generates the interspecific spatial patterns of segregation and partial overlap. Unexpectedly, the species herd protection hypothesis and the low‐frequency hypothesis cannot well explain the mechanism of interspecific interaction at small distances. Resource competition might be responsible for negative associations being more frequent among species pairs.

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