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Figure S1. Expression of 14q32 miRNAs in tumor samples from lung adenocarcinoma patients according to EGFR, KRAS and TP53 mutation status. Figure S2. Methylation analysis of imprinting control regions of the 14q32 cluster in lung adenocarcinoma patients. Figure S3. Association of disease-free survival and N stage in never-smoker lung adenocarcinoma patients. Figure S4. Cell viability of lung adenocarcinoma cells after increasing 14q32 miRNA levels by CRISPR activation technology. Figure S5. Differential expression of genes adjacent to the 14q32 miRNA cluster activated by CRISPR activation technology. Figure S6. Association of genes modulated by 14q32 miRNAs with disease-free survival in lung adenocarcinoma patients. Figure S7. Cell viability of lung adenocarcinoma cells after increasing levels of 14q32 miRNAs by transfection of specific miRNA mimics. Figure S8. Validation of the migratory and invasive effects of miR-323b, miR-487a, and miR-539 on lung adenocarcinoma cells with different genetic background.

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This study was conducted to determine greenhouse gas (GHG) emissions, water consumption, land use, as well as nitrogen (N), phosphorus (P), and carbon (C) balance of five diet formulation strategies and feeding programs for growing-finishing pigs (25-130 kg body weight) in the three spatially explicit geographic regions where the majority of U.S. pork production occurs. Feeding programs evaluated consisted of 1) standard corn-soybean meal (CSBM) diets, 2) CSBM containing 15% corn distillers dried grains with solubles (DDGS), 3) CSBM with 8.6% thermally processed supermarket food waste (FW), 4) low crude protein CSBM diets supplemented with synthetic amino acids (SAA), and 5) CSBM with phytase enzyme (PHY) added at 600 FTU (phytase units)/kg of diet. An attributional Life Cycle Assessment approach using a highly specialized, spatially explicit Food System Supply-Chain Sustainability (FoodS3) model was used to quantify GHG emissions, water consumption, and land use of corn, soybean meal, and DDGS based on county level sourcing. The DDGS, FW, and SAA feeding programs had less estimated N and P intake and excretion than CSBM, and the PHY feeding program provided the greatest reduction in P excretion. The FW feeding program had the least overall GHG emissions (319.9 vs. 324.6 to 354.1 kg CO2 equiv./market hog), land use (331.5 vs. 346.5 to 385.2 m2/market hog), and water consumption (7.64 vs. 7.70 to 8.30 m3/market hog) among the alternatives. The DDGS feeding program had the greatest GHG emissions (354.1 kg CO2 equiv./market hog) among all programs but had less impacts on water consumption (7.70 m3) and land use (346.5 m2) per market hog than CSBM and PHY. The SAA feeding program provided a 6.5-7.4% reduction in land use impacts compared with CSBM and PHY, respectively. Regardless of feeding program, the Midwest had the least contributions to GHG emissions and land use attributed to feed and manure among regions. Water consumption per market hog associated with feeding programs was much greater in the Southwest (59.66-63.58 m3) than in the Midwest (4.45-4.88 m3) and Mid-Atlantic (1.85-2.14 m3) regions. Results show that diet composition and U.S. geographic region significantly affect GHG emissions, water consumption, and land use of pork production systems, and the potential use of thermally processed supermarket food waste at relatively low diet inclusion rates (10%) can reduce environmental impacts compared with other common feeding strategies.Very few studies have been conducted to determine the differences in environmental impacts based on the diet composition of growing-finishing swine feeding programs across major pork production regions in the United States. Therefore, the objective of this study was to determine and compare greenhouse gas (GHG) emissions, water consumption, land use, as well as nitrogen (N), phosphorus (P), and carbon (C) balance of five diet formulation strategies and feeding programs for growing-finishing pigs (25–130 kg body weight) in the three spatially explicit U.S. pork production regions. The corn dried distillers grains with solubles (DDGS), food waste (FW), and low protein-synthetic amino acid (SAA) diets had less estimated N and P excretion compared with corn-soybean meal (CSBM) diets, and the addition of phytase (PHY) to CSBM diets resulted in the greatest reduction in P excretion among feeding programs. Adding FW to diets resulted in the least overall greenhouse gas emissions, water consumption, and land use compared with all other feeding programs, and land use was less for the DDGS and SAA feeding programs than CSBM and PHY feeding programs. The Midwest had the least GHG emissions and land use impact compared with other regions, while the Southwest region had the greatest water consumption associated with feeding programs.

The reuse or sale of byproducts is widespread throughout the global economy. Such byproducts are deemed co-products, while unused byproducts are considered waste. This distinction becomes less clear for waste products that can be turned into useable co-products, creating methodological problems for those studying reuse of byproducts using life cycle assessment, material flow analysis, and input-output analysis. Expanding upon the Rectangular Choice-of-Technologies (RCOT) framework (Duchin and Levine, 2011), this paper presents an approach for associating byproducts from the production process of a primary commodity with a distinct technology. This new RCOT method endogenously defines byproducts as co-products or waste depending on the technological and economic capacity to utilize them. By comparing the prices of utilized co-products to unused wastes, this framework provides an explicit way to relate these three concepts while also illustrating how changing economic conditions can change wastes into co-products, and vice-versa. We present a numerical example of this new method for distiller’s grains byproducts from ethanol production.

This article estimates the amounts of food that is discarded, diverted, and landfilled in Minnesota by comparing and applying approaches and statistics from selected national, regional, and local s...

Recognizing the substantial threats climate change poses to agricultural supply chains, companies around the world are committing to reducing greenhouse gas (GHG) emissions. Recent modeling advances have increased the transparency of meat and ethanol industry supply chains, where conventional production practices and associated environmental impacts have been characterized and linked to downstream points of demand. Yet, to date, information and efforts have neglected both the spatial variability of production impacts and land use changes (LUC) across highly heterogeneous agricultural landscapes. Developing effective mitigation programs and policies requires understanding these spatially-explicit hotspots for targeting GHG mitigation efforts and the links to downstream supply chain actors. Here we integrate, for the first time, spatial estimates of county-scale production practices and observations of direct LUC into company and industry-specific supply chains of beef, pork, chicken, ethanol, soy oil and wheat flour in the U.S., thereby conceptually changing our understanding of the sources, magnitudes and influencers of agricultural GHG emissions. We find that accounting for LUC can increase estimated feedstock emissions per unit of production by a factor of 2- to 5-times that of traditionally used estimates. Substantial variation across companies, sectors, and production regions reveal key opportunities to improve GHG footprints by reducing land conversion within their supply chains.

The combustion of chemicals in engines is much more than a transformation of chemical energy into kinetic energy. Fuel, engine and exhaust gas treatment form a unit with mutual dependencies and optimisation potentials. Above all, the creation of diesel fuels with different biodiesel proportions or biocomponents (Hydrotreated Vegetable Oil, HVO) and raw material provenances is becoming one of the greatest challenges for the petroleum and vehicle industry from a global point of view. But also offers the potential of a timely, based on existing infrastructure, positive climate change. New regenerative fuels entail properties such as polarity, soot mitigation potential and strong solution properties that require optimal formulations, suitable combustion parameters, and chemical resistance of fuel-bearing components. The paper summarizes the most important findings on biofuels and describes the need for action and research, as well as future challenges for biofuels as a pure fuel and blend component from the point of view of business and science.

Corn production, and its associated inputs, is a relatively large source of greenhouse gas emissions and uses significant amounts of water and land, thus contributing to climate change, fossil fuel depletion, local air pollutants, and local water scarcity. As large consumers of this corn, corporations in the ethanol and animal protein industries are increasingly assessing and reporting sustainability impacts across their supply chains to identify, prioritize, and communicate sustainability risks and opportunities material to their operations. In doing so, many have discovered that the direct impacts of their owned operations are dwarfed by those upstream in the supply chain, requiring transparency and knowledge about environmental impacts along the supply chains. Life cycle assessments (LCAs) have been used to identify hotspots of environmental impacts at national levels, yet these provide little subnational information necessary for guiding firms’ specific supply networks. In this paper, our Food System Supply-Chain Sustainability (FoodS3) model connects spatial, firm-specific demand of corn purchasers with upstream corn production in the United States through a cost minimization transport model. This provides a means to link county-level corn production in the United States to firm-specific demand locations associated with downstream processing facilities. Our model substantially improves current LCA assessment efforts that are confined to broad national or state level impacts. In drilling down to subnational levels of environmental impacts that occur over heterogeneous areas and aggregating these landscape impacts by specific supply networks, targeted opportunities for improvements to the sustainability performance of supply chains are identified.

The apparel industry has a tremendous impact on water, yet unlike food systems, where consumer interest in sustainability is growing, it is difficult for the everyday consumer to understand the nuances of sustainable clothing and there has been little growth in sustainability labels and claims. Water use and pollution needs to be evaluated throughout the clothing supply chain to identify leverage points to reduce water impacts and design new processes to integrate water sustainability into production industry-wide.

Inspired by the promising thermoelectric properties of phase-separated half-Heusler materials, we investigated the influence of electron doping in the n-type Ti_(0.3−x)Zr_(0.35)Hf_(0.35)NiSn compound. The addition of Nb to this compound led to a significant increase in its electrical conductivity, and shifted the maximum Seebeck coefficient to higher temperatures owing to the suppression of intrinsic carriers. This resulted in an enhancement of both the power factor α^2σ and figure of merit, zT. The applicability of an average effective mass model revealed the optimized electron properties for samples containing Nb. There is evidence in the literature that the average effective mass model is suitable for estimating the optimized carrier concentration of thermoelectric n-type half-Heusler compounds.

In this Review, the structure, bonding and defects of half-Heusler compounds are explained in terms of the framework of Zintl (or valence-precise) chemistry. This deeper understanding of the structure and electronic properties of half-Heusler compounds should aid the design of improved thermoelectric materials.

SUMMARY Purpose: To assess the efficacy, safety, and tolerability of adjunctive carisbamate treatment at 800 mg/day and 1,200 mg/day in patients with partial-onset seizures (POS). Methods: Patients ‡16 years of age with an established diagnosis of POS for ‡1 year and uncontrolled on one to three antiepileptic drugs were enrolled. Eligible patients remained on stable doses of prescribed antiepileptic drugs for an 8-week pretreatment baseline phase and were then randomized (1:1:1) to receive carisbamate (800 mg/day or 1,200 mg/day), or placebo, for a 14-week double-blind phase. Primaryefficacy endpoints were percentage reduction in POS frequency and responder rate (patients with ‡50%reduction in POS frequency) during the double-blind versus baseline phase. Key Findings: Five hundred forty-seven patients were randomized; 540 composed the intent-to-treat (ITT) analysis. Four hundred thirty-four patients (79%) completed the study. The median percent reduction from baseline to treatment phase in POS frequency was: 21% % (placebo); 30% % (carisbamate 800 mg); 36% % (carisbamate 1,200 mg), and 32% % (combined carisbamate doses). The combined carisbamate dose group was not significantly different from placebo for the median percent reduction of POS frequency (p = 0.20) or responder rate (p = 0.18). Therefore, the difference from placebo for the individual carisbamate dose groups was also considered nonsignificant, based on a prespecified step-down analysis. Dizziness was the most common treatment-emergent adverse event, with a higher incidence (‡5% % difference) in the combined carisbamate group (31%) than placebo (9% %); the incidence was higher with carisbamate 1,200 mg (32% %, n = 58) than with carisbamate 800 mg (30% %, n = 53). Significance: Adjunctive carisbamate therapy in patients with POS did not demonstrate efficacy across the dose range assessed versus placebo. No new safety findings were observed.

Poaching for bushmeat is a major problem for conservation of wildlife populations in many parts of Africa, including the Serengeti ecosystem in Tanzania. However, the severity of the poaching problem is often unclear because of a lack of accurate data. Directly asking people to self-report illegal activity faces the obvious problem of under-reporting. Use of arrest records from anti-poaching patrols may reflect levels of poaching activity but could also be driven by funding and quality of anti-poaching efforts. A third method, assessing poaching by asking about bushmeat consumption, is indirect, possibly subject to under-reporting, and also subject to limits on the accuracy of memory of respondents. We compare rates of poaching derived by self-assessment of poaching activities (based on household interviews), dietary recall of bushmeat consumption over a variety of time frames, and arrest records from anti-poaching units. We apply these three methods to assess poaching activities in three villages bordering protected areas on the western boundary of Serengeti National Park. Our results showed that dietary recall of bushmeat consumption and arrest records indicated similar patterns of poaching across the three villages but self-reporting differed significantly. There appear to be significant advantages to coupling results from dietary recall of bushmeat consumption and arrest records to estimate the level of poaching activity. In situations where reliable data from anti-poaching units are unavailable, cost-effective data collection of bushmeat consumption will provide a viable alternative to assess levels of poaching involvement of villages that border protected areas.

Summary Purpose: To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS). Methods: Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for ≥1 year. Therapy-refractory epilepsy patients (≥16 years) remained on stable doses of prescribed antiepileptic drugs (≤2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ≥50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase. Results: Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16–75 years) and 36 years (study 2, range 16–74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p

N-type XNiSn (X = Ti, Zr, Hf) half-Heusler (HH) compounds possess excellent thermoelectric properties, which are believed to be attributed to their relatively high mobility. However, p-type XNiSn HH compounds have poor figures of merit, zT, compared to XCoSb compounds. This can be traced to the suppression of the magnitude of the thermopower at high temperatures. E_g = 2eS_(max)T_(max) relates the band gap to the thermopower peak. However, from this formula, one would conclude that the band gap of p-type XNiSn solid solutions is only one-third that of n-type XNiSn, which effectively prevents p-type XNiSn HHs from being useful thermoelectric materials. The study of p-type HH Zr_(1−x)Sc_xNiSn solid solutions show that the large mobility difference between electrons and holes in XNiSn results in a significant correction to the Goldsmid–Sharp formula. This finding explains the difference in the thermopower band gap between n-type and p-type HH. The high electron-to-hole weighted mobility ratio leads to an effective suppression of the bipolar effect in the thermoelectric transport properties which is essential for high zT values in n-type XNiSn (X = Ti, Zr, Hf) HH compounds.

The ternary superconductor NaAlSi, isostructural with LiFeAs, the ``111'' iron pnictide superconductor, is investigated under pressure. The structure remains stable up to 15 GPa. Resistivity and susceptibility measurements show an increase of ${T}_{c}$ up to 2 GPa, followed by a decrease until superconductivity disappears at 4.8 GPa. Band structure calculations show that pressure should have a negligible effect on the electronic structure and the Fermi surface and thus the disappearance of superconductivity under pressure must have a different origin. We compare the electronic structure of NaAlSi under pressure with that of nonsuperconducting isostructural NaAlGe.

Copper doping of FeSe destroys its superconductivity at ambient pressure, even at low doping levels. Here we report the pressure-dependent transport and structural properties of Fe${}_{1.01\ensuremath{-}x}$Cu${}_{x}$Se with 3$%$ and 4$%$ Cu doping and find that the superconductivity is restored. Metallic resistivity behavior, absent in Cu-doped FeSe, is also restored. At the low pressure of 1.5 GPa, superconductivity is seen at 6 K for 4$%$ Cu doping, somewhat lower than the 8 K ${T}_{c}$ of undoped FeSe. ${T}_{c}$ reaches its maximum of 31.3 K at 7.8 GPa, lower than the maximum superconducting temperature in the undoped material under pressure (${T}_{c}$ max of 37 K) but still very high. X-ray diffraction shows that applied pressure decreases the lattice parameter in the basal plane, counteracting the structural effect of Cu doping, providing a possible explanation for the restoration of the superconductivity.

Objective: To evaluate the efficacy, safety, and tolerability of carisbamate (CRS), an investigational drug, as adjunctive treatment for partial-onset seizures in adults. Methods: A randomized, double-blind, placebo-controlled, multicenter, dose-ranging study was conducted in 12 countries. Patients counted seizures during an 8-week baseline period, and then, if eligible, entered a double-blind phase consisting of a 4-week dose-titration period (target CRS doses: 100, 300, 800, or 1,600 mg/d or placebo in two divided doses) and a 12-week maintenance period. The primary efficacy variable was percent reduction in partial-onset seizure frequency during the double-blind phase compared with pretreatment baseline. Safety data and responder rates were also assessed. Results: Five hundred thirty-seven patients were randomized, and 82% completed the study. In the intent-to-treat population (n = 533), CRS at doses of ≥300 mg/d ( p ≤ 0.006) reduced the frequency of partial-onset seizures vs placebo: 6% (placebo) vs 24% (300 mg/d), 21% (800 mg/d), and 29% (1,600 mg/d) for CRS. Adverse events consisted primarily of CNS effects, and led to discontinuation of drug in 8% of the placebo group vs 5% (100 mg/d), 6% (300 mg/d), 12% (800 mg/d), and 19% (1,600 mg/d) of the CRS groups. Conclusions: Carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures. GLOSSARY: AED = antiepileptic drug; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRS = carisbamate; LFT = liver function test; TEAE = treatment-emergent adverse event; UGT = uridine diphosphate glucuronosyltransferase.

A substantial proportion of the patient population with migraine headache should be considered for preventive treatment based on the frequency and disability associated with this disorder. Use of the anticonvulsant topiramate was previously examined in two large, double-blind, randomized, placebo-controlled clinical trials of a subset of patients who have 3 to 12 migraine episodes per month.To better characterize the efficacy of topiramate for prevention of migraine, with or without aura, by pooling and analyzing data from the two large clinical trials.The pooled intent-to-treat population included 937 patients receiving topiramate at one of three dosages (50 mg/d, 100 mg/d, 200 mg/d) or placebo. Outcome measures included change in mean monthly migraine frequency and categorical responder rate throughout the 26-week doubleblind phase.At daily doses of 100 and 200 mg, topiramate was associated with significant reductions in mean monthly migraine frequency throughout the double-blind phase compared with placebo (P.001). Significantly more patients treated with these topiramate doses exhibited high-percentage reductions in monthly migraine frequency (/=50% [P.001],/=75% [P.001], 100% [P=.049]) versus placebo. The most common adverse events included anorexia, cognitive deficits, diarrhea, fatigue, nausea, and paresthesia. Topiramate (100 mg/d, 200 mg/d) was associated with significant and sustained reductions in mean monthly migraine frequency beginning as early as 1 week into therapy.Pooled efficacy data from two large, similarly designed, placebo-controlled migraine-prevention trials demonstrated that a statistically significant proportion of patients using topiramate met or exceeded two main outcome guidelines recommended by the International Headache Society (/=50% and/=75% reduction in frequency of monthly attacks). Based on efficacy and tolerability, topiramate at a dosage of 100 mg per day (50 mg twice daily) should be the target dosage for most patients with migraine.

Open-label trials and small controlled studies report topiramate's efficacy in migraine prevention.To assess the efficacy and safety of topiramate as a migraine-preventive therapy.A 26-week, randomized, double-blind, placebo-controlled study.Outpatient treatment at 49 US clinical centers. Patients Patients were aged 12 to 65 years, had a 6-month International Headache Society migraine history, and experienced 3 to 12 migraines per month, but had 15 or fewer headache days per month during the 28-day baseline period.Participants were randomized to placebo or topiramate, 50, 100, or 200 mg/d, titrated by 25 mg/wk to the assigned dose or as tolerated in 8 weeks; maintenance therapy continued for 18 weeks.The primary efficacy assessment was a reduction in mean monthly migraine frequency across the 6-month treatment phase. Secondary end points were responder rate, time to onset of action, mean change in migraine days per month, and mean change in rescue medication days per month.Four hundred eighty-seven patients were randomized, and 469 composed the intent-to-treat population. The mean +/- SD monthly migraine frequency decreased significantly for the 100-mg/d group (from 5.4 +/- 2.2 to 3.3 +/- 2.9; P.001) and the 200-mg/d group (from 5.6 +/- 2.6 to 3.3 +/- 2.9; P.001) vs the placebo group (from 5.6 +/- 2.3 to 4.6 +/- 3.0); improvements occurred within the first treatment month. Significantly more topiramate-treated patients (50 mg/d, 35.9% [P =.04]; 100 mg/d, 54.0% [P.001]; and 200 mg/d, 52.3% [P.001]) exhibited a 50% or more reduction in monthly migraine frequency than placebo-treated patients (22.6%). Adverse events included paresthesia, fatigue, nausea, anorexia, and taste per version.Topiramate, 100 or 200 mg/d, was effective as a preventive therapy for patients with migraine.

Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients withor =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P.001) vs placebo (-1.1). Statistically significant reductions (P.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P.001), and 200 mg/d (47%, P.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.

ContextSmall open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.ObjectiveTo assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.Design, Setting, and PatientsA 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.InterventionsAfter a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.Main Outcome MeasuresThe primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with ≥50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.ResultsOf 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (−2.1, P = .008) and topiramate at 200 mg/d (−2.4, P

This paper investigates demand response implementation in Midwest ISO from the perspective of large energy consumers. Acknowledging uncertain electricity prices, we develop a dynamic programming-based model using real-options theory to identify a profitability threshold for demand response (DR) schemes. Our model is tailored to energy-intensive industries, and the cement industry is used as illustrative example in the case study. Simulation results demonstrate season-dependent profitability threshold for a representative cement manufacturing plant.