Prototyping a Chatbot for Site Managers Using Building Information Modeling (BIM) and Natural Language Understanding (NLU) Techniques.

Amidst the domestic labor shortage and worldwide pandemic in recent years, there has been an urgent need for a digital means that allows construction site workers, particularly site managers, to obtain information more efficiently in support of their daily managerial tasks. For workers who move around the site, traditional software applications that rely on a form-based interface and require multiple finger movements such as key hits and clicks can be inconvenient and reduce their willingness to use such applications. Conversational AI, also known as a chatbot, can improve the ease of use and usability of a system by providing an intuitive interface for user input. This study presents a demonstrative Natural Language Understanding (NLU) model and prototypes an AI-based chatbot for site managers to inquire about building component dimensions during their daily routines. Building Information Modeling (BIM) techniques are also applied to implement the answering module of the chatbot. The preliminary testing results show that the chatbot can successfully predict the intents and entities behind the inquiries raised by site managers with satisfactory accuracy for both intent prediction and the answer. These results provide site managers with alternative means to retrieve the information they need.

Numerosity discrimination in deep neural networks: Initial competence, developmental refinement and experience statistics.

Both humans and non-human animals exhibit sensitivity to the approximate number of items in a visual array, as indexed by their performance in numerosity discrimination tasks, and even neonates can detect changes in numerosity. These findings are often interpreted as evidence for an innate 'number sense'. However, recent simulation work has challenged this view by showing that human-like sensitivity to numerosity can emerge in deep neural networks that build an internal model of the sensory data. This emergentist perspective posits a central role for experience in shaping our number sense and might explain why numerical acuity progressively increases over the course of development. Here we substantiate this hypothesis by introducing a progressive unsupervised deep learning algorithm, which allows us to model the development of numerical acuity through experience. We also investigate how the statistical distribution of numerical and non-numerical features in natural environments affects the emergence of numerosity representations in the computational model. Our simulations show that deep networks can exhibit numerosity sensitivity prior to any training, as well as a progressive developmental refinement that is modulated by the statistical structure of the learning environment. To validate our simulations, we offer a refinement to the quantitative characterization of the developmental patterns observed in human children. Overall, our findings suggest that it may not be necessary to assume that animals are endowed with a dedicated system for processing numerosity, since domain-general learning mechanisms can capture key characteristics others have attributed to an evolutionarily specialized number system.

MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics.

PURPOSE: MITOsym, a new mathematical model of hepatocellular respiration and bioenergetics, has been developed in partnership with the DILIsym® model with the purpose of translating in vitro compound screening data into predictions of drug induced liver injury (DILI) risk for patients. The combined efforts of these two models should increase the efficiency of evaluating compounds in drug development in addition to enhancing patient care. METHODS: MITOsym includes the basic, essential biochemical pathways associated with hepatocellular respiration and bioenergetics, including mitochondrial oxidative phosphorylation, electron transport chain activity, mitochondrial membrane potential, and glycolysis; also included are dynamic feedback signals based on perturbation of these pathways. The quantitative relationships included in MITOsym are based primarily on published data; additional new experiments were also performed in HepG2 cells to determine the effects on oxygen consumption rate as media glucose concentrations or oligomycin concentrations were varied. The effects of varying concentrations of FCCP on the mitochondrial proton gradient were also measured in HepG2 cells. RESULTS: MITOsym simulates and recapitulates the reported dynamic changes to hepatocellular oxygen consumption rates, extracellular acidification rates, the mitochondrial proton gradient, and ATP concentrations in the presence of classic mitochondrial toxins such as rotenone, FCCP, and oligomycin. CONCLUSIONS: MITOsym can be used to simulate hepatocellular respiration and bioenergetics and provide mechanistic hypotheses to facilitate the translation of in vitro data collection to predictions of in vivo human hepatotoxicity risk for novel compounds.

Conjugative metabolism of 1,2-dibromoethane in mitochondria: disruption of oxidative phosphorylation and alkylation of mitochondrial DNA.

1,2-Dibromoethane (DBE) is an environmental contaminant that is metabolized by glutathione S-transferases to a haloethane-glutathione conjugate. Since haloethane-glutathione conjugates are known to alkylate nuclear DNA and cytoplasmic proteins, these effects were investigated in isolated rat liver mitochondria exposed to DBE by measuring guanine adducts and several aspects of oxidative phosphorylation including respiratory control ratios, respiratory enzyme activity, and ATP levels. Mitochondrial large-amplitude swelling and glutathione status were assessed to evaluate mitochondrial membrane integrity and function. When exposed to DBE, mitochondria became uncoupled rapidly, yet no large-amplitude swelling or extramitochondrial glutathione was observed. Mitochondrial GSH was depleted to 2-53% of controls after a 60-min exposure to micromolar quantities of DBE; however, no extramitochondrial GSH or GSSG was detected. The depletion of mitochondrial glutathione corresponded to an increase of an intramitochondrial GSH-conjugate which, based on HPLC elution profiles and retention times, appeared to be S,S'-(1,2-ethanediyl)bis(glutathione). Activities of the NADH oxidase and succinate oxidase respiratory enzyme systems were inhibited 10-74% at micromolar levels of DBE, with succinate oxidase inactivation occurring at lower doses. ATP concentrations in DBE-exposed mitochondria in the presence of succinate were 5-90% lower than in the controls. The DNA adduct S-[2-(N(7)-guanyl)ethyl]glutathione was detected by HPLC in mtDNA isolated from DBE-exposed mitochondria. The results suggest that respiratory enzyme inhibition, glutathione depletion, decreased ATP levels, and DNA alkylation in DBE-exposed mitochondria occur via the formation of an S-(2-bromoethyl)glutathione conjugate, the precursor of the episulfonium ion alkylating species of DBE.

Overview of glutathione function and metabolism.

Glutathione is a key player in reduction processes in the cell. It is responsible for maintaining thiol groups of intracellular proteins by providing reducing power for cysteine, dihydolipoate, CoA, ascorbate, and vitamin E. It also plays a role in reduction of NTPs to dNTPs. Glutathione is also involved in detoxification of endogenous and exogenous compounds, participates in the synthesis of leukotrienes and prostaglandins, serves as a cofactor for various enzymes, stores and transports cysteine, and may be involved in cell cycle regulation and thermotolerance.

gamma-glutamyltranspeptidase-deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular function.

gamma-Glutamyltranspeptidase (GGT)-deficient mice (GGT(-/-)) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by >/=50% in GGT(-/-) mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT(-/-) mice liver mitochondria were /=40% in mitochondria obtained from GGT(-/-) mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT(-/-) knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT(-/-) mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT(-/-) mice with N-acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT(-/-) mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice.

Gamma-glutamyltranspeptidase knockout mice as a model for understanding the consequences of diminished glutathione on T cell-dependent immune responses.

Gamma-Glutamyltranspeptidase (GGT) catalyzes the first step in the extracellular hydrolysis of glutathione (GSH) and plays a critical role in GSH recycling; however, little is known about the impact of diminished GGT activity on immune function. We report here that GGT knockout (GGT(-/-)) mice have a 30 % decrease in splenic GSH and a 50 % reduction in thymus and spleen cellularity. The decreased cellularity was not selective for one population of cells, as each population was equivalently reduced. Following antigen challenge, GSH levels were reduced by 20-40 % in CD4+ and CD8+ T cells from GGT(-/-) mice when compared to T cells from wild-type mice. To test whether decreased GSH impairs immunity, we examined immune responsiveness following in vivo challenge with four different T cell-dependent stimuli. While there was no alteration in the antibody response to ovalbumin and sheep erythrocytes, cytotoxic T lymphocyte and alloantibody activity against P815 cells were decreased by 30 % and 65 %, respectively. Compared to wild-type littermates, anti-CD3-induced IL-2 and IL-6 production were also diminished in GGT(-/-) mice. These results demonstrate differential effects of decreased GSH on in vivo immune responsiveness to distinct stimuli, and suggest an important immunoregulatory role for GSH.

Role of gonadal steroids in determining sexual differences in expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the hypothalamic arcuate nucleus.

Dual immunohistochemistry was employed to examine the role of gonadal steroids in determining sexual differences in the expression of Fos and its related antigens (FRA) in tuberoinfundibular dopaminergic (TIDA) neurons located in the dorsomedial (DM-) and ventrolateral (VL-) subdivisions of the arcuate nucleus (ARC). In the DM-ARC, there was no sexual difference in the number of tyrosine hydroxylase (TH)-immunoreactive (-IR) perikarya, but the number of these containing FRA-IR was greater in females than in males in all but the most caudal region. In the VL-ARC, there were more TH-IR perikarya in males than in females, but there was no sexual difference in the numbers of those containing FRA-IR throughout the entire rostrocaudal extent of this nucleus. Ovariectomy decreased the number of TH-IR perikarya containing FRA-IR in the DM-ARC, but not in the VL-ARC, whereas orchidectomy increased the number of TH-IR perikayra containing FRA-IR in both the DM-ARC and VL-ARC. These gonadectomy-induced effects were reversed by estrogen and testosterone, respectively. These results reveal gonadal steroid-dependent sexual differences in the regulation of immediate early gene expression in anatomically discrete subpopulations of TIDA neurons. In females, estrogen stimulates FRA expression in TIDA neurons in the DM-ARC, whereas in males, testosterone inhibits FRA expression in TIDA neurons in both the DM-ARC and the VL-ARC.

[Reference values for cortisol, T4 and T-uptake in different horse groups using the fluorescence polarization immunoassay (FPIA)]. / Referenzwerte für Cortisol, T4 and T-Uptake bei verschiedenen Pferdegruppen bestimmt mittels Fluoreszenz-Polarisations-Immunoassays (FPIAs).

Reference values for Cortisol, T4 and T-Uptake, determined with the Fluorescence-Polarization-Immunoassays (FPIAs) in blood-plasma of different horse groups were established. The highest Cortisol values were measured in blood samples from thoroughbred racehorses and riding horses taken between 7 and 8 a.m. (181 +/- 37 and 268 +/- 43 nmol/l), the lowest gained between 5 and 6 p.m. (69 +/- 45 and 85 +/- 32 nmol/l respectively). Peak values for T4 in riding horses were found in blood samples collected between 1 and 2 p.m. (28.2 +/- 5.7 nmol/l) followed by the samples taken at 5-6 p.m. and 7-8 a.m. T-Uptake values did not show a diurnal variation. Values of thoroughbred racehorses were much lower than in thoroughbred broodmares and riding horses (0.11 +/- 0.03, 0.18 +/- 0.03 and 0.24 +/- 0.05 units). The blood samples collected on 5 successive days showed significant variations for Cortisol. T4-values were stable whilst T-Uptake had small variations.

[Determination of cortisol, T4, T3 and T-uptake in serum and plasma of horses using fluorescence polarization immunoassays (FIPAs)]. / Cortisol, T4, T3 und T-uptake-Bestimmung in Serum und Plasma von Pferden mittels Fluoreszenz-Polarisations-Immunoassays (FPIAs).

The influence of duration and temperature of storage on hormone levels of whole blood, plasma and serum of horses was investigated. Using FPIAs cortisol, T4 and T-uptake could be measured while the T3-FPIA did not work appropriately. Serum and Plasma stored under the same conditions did not show any difference in cortisol, T4 and T-uptake values. In frozen heparinized plasma samples analysed on different days the cortisol and T4 concentrations fluctuated markedly. The T-uptake values were rather stable. The smallest day by day changes of cortisol and T4 in plasma were found when storing the samples at 20-22 degrees C. At 4 degrees C cortisol decreased markedly while for T4 a clear trend was not found. The cortisol concentration in whole blood stored at 4 degrees C decreased more markedly than in samples stored at 20-22 degrees C. T4 remained stable in whole blood samples stored at 20-22 degrees C over 4 days while showing fluctuations in samples stored at 4 degrees C.