Miracle-dz/UniFAR-FTUs huggingface dataset:
Capacitated Two-Stage Multi-Item Production/Inventory Model with Joint Setup Costs

We analyze a continuous-time, two-stage production/inventory system. In the first stage, a common intermediate product is produced in batches, and possibly stored. In the second phase, the intermediate product is fabricated into n distinct finished products. Several finished products may be included in a single production batch of limited capacity to exploit economies of scale. We propose a planning methodology to address the combined problem of joint setup costs and capacity limits per setup. We restrict ourselves to a class of replenishment strategies with the following properties: a replenishment strategy specifies a collection of families subsets of items covering all end-items, if an item belongs to several families a specific fraction of its sales is assigned to each family. Each time the inventory of one item in a family is replenished, the inventories of all other items in the family are replenished as well. We derive a simple roughly 0n log n algorithm that results in a strategy whose long-run average cost comes within a few percentage points of a lower bound for the minimum achievable cost within the above class of strategies.
Buttressing regulation of cognitive enhancement devices with principles of harm reduction

Maslen and colleagues offer an excellent model for regulating cognitive enhancement devices (CEDs), and we largely endorse their approach of extending medical device policy to include CEDs. Maslen et al. argue that since the risks and benefits of CEDs can be identified, consumers are best placed to evaluate the impact of these effects on their own wellbeing: ‘experts are to assess what the risks are, the consumer how much they matter’. In principle, we agree: consumers should be allowed to decide what risks are worth taking, but the situation is somewhat more complicated, for the evidence that consumers are in a strong position to evaluate the many risks associated with CED use is lacking. Indeed, a glance at online forums on CEDs suggests that undue risks are already being taken. Importantly, given the ease with which devices can be built using easily obtainable parts, overly tough regulation will not effectively curtail use, but rather push it underground. For these reasons, we suggest that any regulatory framework be buttressed by principles of harm reduction, providing real-world users with expert-backed recommendations for safe use. We argue for the development of tools that facilitate this dialogue, while recognizing the challenges in so doing.
Familial juvenile parkinsonism

We describe a family with juvenile-onset parkinsonism, which improved following sleep. Four of the five siblings in this family developed a similar onset of parkinsonism at an early age, and the parents were first cousins. In one of the siblings, a 67-year-old woman, pathologic changes at autopsy were confined to the substantia nigra pars compacta (SNPC) and locus ceruleus. The SNPC revealed obvious neuronal loss and gliosis in the medial and ventrolateral regions. In the remainder of the SNPC and the locus ceruleus, the population of neurons was reduced and there was low melanin content in most of the neurons but no detectable gliosis or extraneuronal free melanin pigment suggestive of a neurodegenerative process. There were no Lewy bodies. The entire pathologic picture was different from that of Lewy body Parkinson's disease.
Adaptive Sub-Threshold Test Circuit

Emerging ubiquitous systems such as distributed sensor networks require ultra-low power consumption. The energy minimum and thus, the lowest possible power consumption of CMOS logic, is achieved in the sub-threshold region. The exponential dependence of the drain current on threshold voltage variations leads to increased overdesign if sub-threshold circuits are to be robust. Adaptive systems are required to address variability robustness. One approach to achieve adaptivity is timing error detection (TED) within the circuit. Presented here is a TED latch capable of sub-threshold operation. It was designed in 65 nm technology, has an operating voltage range of 0.25 V through 1.2 V, and a minimum energy point (MEP) of 0.4 V. At the MEP, the average power consumption for one clock period and an activity factor of alpha=0.5 is 0.43 nW. The area of the TED latch is 101 um^2. A sub-threshold CORDIC implementation is presented to demonstrate the TED latch at a system level.
Repair of damaged intestinal mucosa in a mouse model of sepsis

BACKGROUND: The intestine is not only the main target attacked by sepsis but also the vital organ which mediated sepsis. The recovery of the damaged intestinal barrier structure and function is related to the occurrence and outcome of multiple organ dysfunction syndrome (MODS). How to protect and reduce the damage of the intestinal mucosa and how to promote the reconstruction of the intestinal mucosa have been the important topics in sepsis for many years. This study aimed to investigate the influential factors of intestinal mucosal reconstruction after intestinal epithelial injury in vivo in a mouse model of sepsis. METHODS: Mice were subjected to cecal ligation and puncture (CLP) for induction of sepsis to assess intestinal mucosal damage, epithelial cell apoptosis, and transformed number of goblet cells, and to detect the concentration of TNF-α, IL-1 and TGF-β1 and TFF3 (trefoil factor 3) expression in the small intestinal mucosa. All above were performed by HE staining, western blot, ELISA and immunohistochemistry respectively. The experimental animals were divided into a sepsis group and a sham-operation group. The animals with sepsis were separately killed at 6 (7 animals), 24 (7 animals) and 48 hours (7 animals) after CLP. RESULTS: Injured intestinal mucosa was observed in the 3 groups under a light microscope, in which damage scores in the 24-hour and 48-hour groups were higher than in the 6-hour group and no difference was found between the two groups. Moreover, less of goblet cells or other epithelial cells adjacent to the injured surface migrated into the wound to cover the denuded area. The number of goblet cells was substantially decreased in the three CLP groups compared with the sham-operation group. Protein levels of IL-1 and TNF-α were significantly increased by 3–4 fold at all time points when compared with the sham-operation group, and cleaved caspase-3 by 4 fold. Although TFF3 expression was modestly increased for 6 hours after the onset of CLP, it appeared to decline at 24 hours and 48 hours as shown by Western blot. A similar tendency was observed upon TGF-β1, i.e. the protein level was not elevated at 24 hours and 48 hours, but increased modestly at 6 hours. CONCLUSIONS: Sepsis from CLP shows less restitution on the surface of injured intestinal mucosa. There is evidence that both constant inflammatory reaction and epithelial cell apoptosis may affect mucosal reestablishment of the intestine at the onset of sepsis. Mucosa after severe sepsis showed the state of high inflammation, and declined goblet cell function and mucosal reconstruction, which affected the repair of damaged intestinal barrier. Constant inflammatory reaction, and declined goblet cell function and mucosal reconstruction ability may affect the reestablishment of intestinal mucosa at the onset of sepsis.
Major Challenges and Potential Microenvironment-Targeted Therapies in Glioblastoma

Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF–VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM. Potential combination therapies targeting the tumor microenvironment (TME) to overcome the myeloid cell-mediated resistance problem in GBM are discussed. Future directions are focused on the use of TME-directed therapies in combination with standard therapy in clinical trials, and the exploration of novel therapies and GBM models for preclinical studies. We believe this review will guide the future of GBM research and therapy.
Studying user browsing behavior through gamified search tasks

Typical crowdsourcing tasks ask workers to label images or make relevance judgements, as a low cost alternative to lab based user studies. More recently, gamification has been employed as a way to make these tasks more appealing and so users play, rather than work. One observation is that differences in task design and incentives elicits different player behavior. In this paper we discuss a new type of task, where we aim at eliciting player behavior that resembles user behavior when performing a search task. Care should be taken in the design of a gamified version of such a task to allow players to complete tasks with a limited amount of effort and time, without changing the behavior to be studied. We discuss the motivation of the abstractions and design choices we have made in achieving this goal. We then analyze whether and how these abstractions and design choices influence our observations of player behaviors.
Mechanisms of ictogenesis in an experimental model of temporal lobe seizures

Experimental Neurophysiology Labs. Istituto Neurologico C. Besta, MILAN. - Laboratori NEST (Nanoscale Engineering Science and Technology Laboratory). Istituto di Neuroscienze CNR, PISA. A part of this thesis was originally published in: Gnatkovsky, V. ; Librizzi, L. ; Trombin, F. and de Curtis, M. (2008) Inhibitory networks support fast activity at seizure onset in the entorhinal cortex of the in vitro isolated guinea pig brain. Annals of Neurology 64 (6) 674-686 http://dx.doi. org/10.1002/ana.21519 ©2008 WILEY
Selection for increased weaning or yearling weight in Hereford cattle. II. Direct and correlated responses.

Selection was applied from 1964 to 1978 for increased weaning weight (WWL) or yearling weight (YWL) in two Hereford lines. An Angus line was maintained as an unselected control line (CL). Each line was maintained with 50 cows and four sires each year (two sires selected each year and used for 2 yr). Primary traits measured in the lines were birth weight (BW), preweaning daily gain (WDG), weaning weight (WW), weaning conformation grade (WG), weaning condition score (WC), weaning to yearling daily gain (YDG), yearling weight (YW), yearling conformation grade (YG) and yearling condition score (YC). Averaged over two methods, estimated genetic responses/generation (in standard deviation units) in WWL and YWL were: BW, . 29, . 26; WDG, . 17, . 15; WW, . 22, . 19; WG, . 19, . 26; WC, . 12, . 12; YDG, -. 02, . 04; YW, . 08, . 14; YG, . 19, . 16; YC, -. 13, -. 03. The realized heritability estimates were . 23 and . 15 for WW and YW, respectively. The realized genetic correlation between WW and YW was . 69. Progeny from crosses of selected WWL and YWL sires to Angus cows had similar feedlot and carcass performance. At the end of the study, milk yield and composition were similar for mature cows in WWL and YWL.
Blood Oxygen Level-Dependent Activation of the Primary Visual Cortex Predicts Size Adaptation Illusion

In natural scenes, objects rarely occur in isolation but appear within a spatiotemporal context. Here, we show that the perceived size of a stimulus is significantly affected by the context of the scene: brief previous presentation of larger or smaller adapting stimuli at the same region of space changes the perceived size of a test stimulus, with larger adapting stimuli causing the test to appear smaller than veridical and vice versa. In a human fMRI study, we measured the blood oxygen level-dependent activation (BOLD) responses of the primary visual cortex (V1) to the contours of large-diameter stimuli and found that activation closely matched the perceptual rather than the retinal stimulus size: the activated area of V1 increased or decreased, depending on the size of the preceding stimulus. A model based on local inhibitory V1 mechanisms simulated the inward or outward shifts of the stimulus contours and hence the perceptual effects. Our findings suggest that area V1 is actively involved in reshaping our perception to match the short-term statistics of the visual scene.
Proteome profiling of heat, oxidative, and salt stress responses in Thermococcus kodakarensis KOD1

The thermophilic species, Thermococcus kodakarensis KOD1, a model microorganism for studying hyperthermophiles, has adapted to optimal growth under conditions of high temperature and salinity. However, the environmental conditions for the strain are not always stable, and this strain might face different stresses. In the present study, we compared the proteome response of T. kodakarensis to heat, oxidative, and salt stresses using two-dimensional electrophoresis, and protein spots were identified through MALDI-TOF/MS. Fifty-nine, forty-two, and twenty-nine spots were induced under heat, oxidative, and salt stresses, respectively. Among the up-regulated proteins, four proteins (a hypothetical protein, pyridoxal biosynthesis lyase, peroxiredoxin, and protein disulphide oxidoreductase) were associated with all three stresses. Gene ontology analysis showed that these proteins were primarily involved metabolic and cellular processes. The KEGG pathway analysis suggested that the main metabolic pathways involving these enzymes were related to carbohydrate metabolism, secondary metabolite synthesis, and amino acid biosynthesis. These data might enhance our understanding of the functions and molecular mechanisms of thermophilic Archaea for survival and adaptation in extreme environments.
Reproductive Health Risks Associated With Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

Objectives:Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods:A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results:Although effect sizes varied with study size and population, occupational exposure to antineoplastic drugs seems to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time to pregnancy also suggested an increased risk for subfertility. Conclusions:Antineoplastic drugs are highly toxic in patients receiving treatment, and adverse reproductive effects have been well documented in these patients. Health care workers with long-term, low-level occupational exposure to these drugs also seem to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered.
Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network

Calcium-dependent activator protein for secretion 2 (CAPS2) is a dense-core vesicle-associated protein that is involved in the secretion of BDNF. BDNF has a pivotal role in neuronal survival and development, including the development of inhibitory neurons and their circuits. However, how CAPS2 affects BDNF secretion and its biological significance in inhibitory neurons are largely unknown. Here we reveal the role of CAPS2 in the regulated secretion of BDNF and show the effect of CAPS2 on the development of hippocampal GABAergic systems. We show that CAPS2 is colocalized with BDNF, both synaptically and extrasynaptically in axons of hippocampal neurons. Overexpression of exogenous CAPS2 in hippocampal neurons of CAPS2-KO mice enhanced depolarization-induced BDNF exocytosis events in terms of kinetics, frequency, and amplitude. We also show that in the CAPS2-KO hippocampus, BDNF secretion is reduced, and GABAergic systems are impaired, including a decreased number of GABAergic neurons and their synapses, a decreased number of synaptic vesicles in inhibitory synapses, and a reduced frequency and amplitude of miniature inhibitory postsynaptic currents. Conversely, excitatory neurons in the CAPS2-KO hippocampus were largely unaffected with respect to field excitatory postsynaptic potentials, miniature excitatory postsynaptic currents, and synapse number and morphology. Moreover, CAPS2-KO mice exhibited several GABA system-associated deficits, including reduced late-phase long-term potentiation at CA3–CA1 synapses, decreased hippocampal theta oscillation frequency, and increased anxiety-like behavior. Collectively, these results suggest that CAPS2 promotes activity-dependent BDNF secretion during the postnatal period that is critical for the development of hippocampal GABAergic networks.
Prophylactic Dexamethasone Decreases the Incidence of Sore Throat and Hoarseness After Tracheal Extubation with a Double-Lumen Endobronchial Tube

BACKGROUND:Postoperative sore throat and hoarseness are common complications after tracheal intubation, particularly after using a double-lumen endobronchial tube (DLT). We conducted a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy of dexamethasone for reducing the incidence and severity of postoperative sore throat and hoarseness. METHODS:One hundred sixty-six patients (aged 18–75 yr) scheduled for thoracic surgery with a DLT were enrolled. Before induction of general anesthesia, 0.1 mg/kg dexamethasone (Group D1), 0.2 mg/kg dexamethasone (Group D2), or a placebo (Group P) were infused IV in a double-blind and prospectively randomized manner. Glottic exposure as defined by Cormack and Lehane score, resistance to DLT insertion, number of intubation attempts, time to achieve intubation, and the duration of tracheal intubation were recorded. At 1 h and 24 h after tracheal extubation, the patients were evaluated for sore throat and hoarseness using a visual analog scale (VAS; where 0 = no pain and 100 = worst pain imaginable). RESULTS:One hour after tracheal extubation, the incidence of postoperative sore throat and hoarseness, along with the severity of sore throat were lower in Group D1 (31%, P = 0.021; 11%, P = 0.003; and VAS 12.4, P < 0.001, respectively) and D2 (11%, P = 0.001; 4%, P = 0.001; and VAS 6.6, P < 0.001, respectively) compared with Group P (53%, 36% and VAS 30.9, respectively). Twenty-four hours after tracheal extubation, the incidence of postoperative sore throat, hoarseness, and the severity of sore throat were significantly lower in Group D2 (27%, P = 0.002; 15%, P = 0.001; and VAS 29.9, P < 0.002, respectively) compared with Group D1 (47%, 31%, and VAS = 43.9, respectively) and Group P (57%, 45%, and VAS = 51.3, respectively). There was no complication associated with the dexamethasone administration. CONCLUSION:The prophylactic use of 0.2 mg/kg of dexamethasone significantly decreases the incidence and severity of sore throat and hoarseness 1 h and 24 h after tracheal extubation of a DLT.
Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme.

CONTEXT St John's wort is a popular herbal product used to treat depression but it has been implicated in drug interactions. OBJECTIVE To assess the potential of St John's wort administration to alter the activity of the cytochrome P450 (CYP) enzymes extensively involved in drug metabolism. DESIGN, SETTING, AND PARTICIPANTS Open-label crossover study with fixed treatment order conducted March 2002 to February 2003 in a US general clinical research center involving 12 healthy volunteers (6 men and 6 women) aged 22 to 38 years before and after 14 days of administration of St John's wort. INTERVENTION Participants were given probe drugs (30 mg of dextromethorphan and 2 mg of alprazolam) to establish baseline CYP 3A4 and CYP 2D6 activity. After a minimum 7-day washout period, participants began taking one 300-mg tablet 3 times per day. After 14 days of St John's wort administration, participants were given the probe drugs along with 1 St John's wort tablet to establish postadministration CYP activity; the St John's wort dosing regimen was continued for 48 hours. MAIN OUTCOME MEASURES Changes in plasma pharmacokinetics of alprazolam as a probe for CYP 3A4 activity and the ratio of dextromethorphan to its metabolite, dextrorphan, in urine as a probe for CYP 2D6 activity. RESULTS A 2-fold decrease in the area under the curve for alprazolam plasma concentration vs time (P<.001) and a 2-fold increase in alprazolam clearance (P<.001) were observed following St John's wort administration. Alprazolam elimination half-life was shortened from a mean (SD) of 12.4 (3.9) hours to 6.0 (2.4) hours (P<.001). The mean (SD) urinary ratio of dextromethorphan to its metabolite was 0.006 (0.010) at baseline and 0.014 (0.025) after St John's wort administration (P =.26). CONCLUSIONS A 14-day course of St John's wort administration significantly induced the activity of CYP 3A4 as measured by changes in alprazolam pharmacokinetics. This suggests that long-term administration of St John's wort may result in diminished clinical effectiveness or increased dosage requirements for all CYP 3A4 substrates, which represent at least 50% of all marketed medications.
Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity

Significance Pseudomonas aeruginosa is the major respiratory pathogen that promotes disease progression in chronic lung diseases such as cystic fibrosis (CF) and resides in antibiotic-resistant biofilm communities in the lungs of patients. Little is known about host factors that contribute to the development of bacterial biofilms in the lung. We have observed that respiratory virus coinfection and the antiviral immune response aid in the transition of P. aeruginosa to a biofilm mode of growth through inappropriate release of the nutrient iron. Defining molecular mechanisms by which P. aeruginosa biofilms develop in the lung affords a better opportunity to target therapies to eliminate life-threatening infections in CF and in other chronic lung diseases. Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients’ acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.