Single machine scheduling with general positional deterioration and rate-modifying maintenance

We present polynomial-time algorithms for single machine problems with generalized positional deterioration effects and machine maintenance. The decisions should be taken regarding possible sequences of jobs and on the number of maintenance activities to be included into a schedule in order to minimize the overall makespan. We deal with general non-decreasing functions to represent deterioration rates of job processing times. Another novel extension of existing models is our assumption that a maintenance activity does not necessarily fully restore the machine to its original perfect state. In the resulting schedules, the jobs are split into groups, a particular group to be sequenced after a particular maintenance period, and the actual processing time of a job is affected by the group that job is placed into and its position within the group

Single machine scheduling with a generalized job-dependent cumulative effect

We consider a single machine scheduling problem with changing processing times. The processing conditions are subject to a general cumulative effect, in which the processing time of a job depends on the sum of certain parameters associated with previously scheduled jobs. In previous papers, these parameters are assumed to be equal to the normal processing times of jobs, which seriously limits the practical application of this model. We further generalize this model by allowing every job to respond differently to these cumulative effects. For the introduced model, we solve the problem of minimizing the makespan, with and without precedence constraints. For the problem without precedence constraints, we also consider a situation in which a maintenance activity is included in the schedule, which can improve the processing conditions of the machine, not necessarily to its original state. The resulting problem is reformulated as a variant of a Boolean programming problem with a quadratic objective, known as a half-product, which allows us to develop a fully polynomial-time approximation scheme with the best possible running time

Approximation schemes for scheduling on a single machine subject to cumulative deterioration and maintenance

We consider a scheduling problem on a single machine to minimize the makespan. The processing conditions are subject to cumulative deterioration, but can be restored by a single maintenance. We link the problem to the Subset-sum problem (if the duration of maintenance is constant) and to the Half-Product Problem (if the duration of maintenance depends on its start time). For both versions of the problem, we adapt the existing fully polynomial-time approximation schemes to our problems by handling the additive constants

Single machine scheduling with time-dependent linear deterioration and rate-modifying maintenance

We study single machine scheduling problems with linear time-dependent deterioration effects and maintenance activities. Maintenance periods (MPs) are included into the schedule, so that the machine, that gets worse during the processing, can be restored to a better state. We deal with a job-independent version of the deterioration effects, that is, all jobs share a common deterioration rate. However, we introduce a novel extension to such models and allow the deterioration rates to change after every MP. We study several versions of this generalized problem and design a range of polynomial-time solution algorithms that enable the decision-maker to determine possible sequences of jobs and MPs in the schedule, so that the makespan objective can be minimized. We show that all problems reduce to a linear assignment problem with a product matrix and can be solved by methods very similar to those used for solving problems with positional effects

Combining time and position dependent effects on a single machine subject to rate-modifying activities

We introduce a general model for single machine scheduling problems, in which the actual processing times of jobs are subject to a combination of positional and time-dependent effects, that are job-independent but additionally depend on certain activities that modify the processing rate of the machine, such as, maintenance. We focus on minimizing two classical objectives: the makespan and the sum of the completion times. The traditional classification accepted in this area of scheduling is based on the distinction between the learning and deterioration effects on one hand, and between the positional effects and the start-time dependent effects on the other hand. Our results show that in the framework of the introduced model such a classification is not necessary, as long as the effects are job-independent. The model introduced in this paper covers most of the previously known models. The solution algorithms are developed within the same general framework and their running times are no worse than those available earlier for problems with less general effects

A fast FPTAS for single machine scheduling problem of minimizing total weighted earliness and tardiness about a large common due date

We address the single machine scheduling problem to minimize the total weighted earliness and tardiness about a nonrestrictive common due date. This is a basic problem with applications to the just-in-time manufacturing. The problem is linked to a Boolean programming problem with a quadratic objective function, known as the half-product. An approach to developing a fast fully polynomial-time approximation scheme (FPTAS) for the problem is identified and implemented. The running time matches the best known running time for an FPTAS for minimizing a half-product with no additive constan

Refined conditions for V-shaped optimal sequencing on a single machine to minimize total completion time under combined effects

We address single machine scheduling problems for which the actual processing times of jobs are subject to various effects, including a positional effect, a cumulative effect and their combination. We review the known results on the problems to minimize the makespan, the sum of the completion times and their combinations and identify the problems for which an optimal sequence cannot be found by simple priority rules such as SPT (Shortest Processing Time) and/or LPT (Longest Processing Time). Typically, these are problems to minimize the sum of the completion times under a deterioration effect, and we verify under which conditions for these problems an optimal permutation is V-shaped (an LPT subsequence followed by an SPT subsequence). We demonstrate that previously used techniques for proving that an optimal sequence is V- shaped are not properly justified. We use the corrected method to describe a wide range of problems with a pure positional effect and a combination of a cumulative effect with a positional effect for which an optimal sequence is V-shaped. On other hand, we show that even the refined approach has its limitations

Converging evidence points towards a role of insulin signaling in regulating compulsive behavior.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

There is a paucity of efficacious new compounds to treat neuropsychiatric disorders. We present a novel approach to neuropsychiatric drug discovery based on high-content characterization of druggable signaling network responses at the single-cell level in patient-derived lymphocytes ex vivo. Primary T lymphocytes showed functional responses encompassing neuropsychiatric medications and central nervous system ligands at established (e.g., GSK-3?) and emerging (e.g., CrkL) drug targets. Clinical application of the platform to schizophrenia patients over the course of antipsychotic treatment revealed therapeutic targets within the phospholipase C?1-calcium signaling pathway. Compound library screening against the target phenotype identified subsets of L-type calcium channel blockers and corticosteroids as novel therapeutically relevant drug classes with corresponding activity in neuronal cells. The screening results were validated by predicting in vivo efficacy in an independent schizophrenia cohort. The approach has the potential to discern new drug targets and accelerate drug discovery and personalized medicine for neuropsychiatric conditions

A machine learning algorithm to differentiate bipolar disorder from major depressive disorder using an online mental health questionnaire and blood biomarker data.

The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score ≥5) aged 18-45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86-0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86-0.91) and 0.90 (0.87-0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57-0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD