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Supplemental 3. Radiation temporarily increases tumor resident MDSC population in MycCap tumors

Supplemental 4. anti-Gr-1 eradiated MDSC in spleen, blood and tumor.

Supplementary Figure S1, S2, S3, S4, S5, S6, S7

Supplemental 5. anti-Gr-1 increased PD-1 expression.

Supplemental 1. RT 2x 8Gy inhibited tumor growth in MycCap animals

Resection surgery of lymph node metastasis of PC3-PSCA-fluc tumor with fluorescence navigation by A11 Mb-IRDye800CW

Purpose:The inability to intraoperatively distinguish primary tumor, as well as lymphatic spread, increases the probability of positive surgical margins, tumor recurrence, and surgical toxicity. The goal of this study was to develop a tumor-specific optical probe for real-time fluorescence-guided surgery.Experimental Design:A humanized antibody fragment against PSCA (A11 minibody, A11 Mb) was conjugated with a near-infrared fluorophore, IRDye800CW. The integrity and binding of the probe to PSCA were confirmed by gel electrophoresis, size-exclusion chromatography, and flow cytometry, respectively. The ability of the probe to detect tumor-infiltrated lymph nodes and metastatic lesions was evaluated in 2 xenograft models, as well as in transgenic mice expressing human PSCA (hPSCA). An invasive intramuscular model was utilized to evaluate the efficacy of the A11 Mb-IRDye800CW-guided surgery.Results:A11 Mb was successfully conjugated with IRDye800CW and retained specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 48 hours. The A11 Mb-IRDye800CW specifically detected PSCA-positive primary tumors, tumor-infiltrated lymph nodes, and distant metastases with high contrast. Fluorescence guidance facilitated more complete tumor resection, reduced tumor recurrence, and improved overall survival, compared with conventional white light surgery. The probe successfully identified primary orthotopic tumors and metastatic lesions in hPSCA transgenic mice.Conclusions:Real-time fluorescence image–guided surgery with A11 Mb-IRDye800CW enabled detection of lymph node metastases and positive surgical margins, facilitated more complete tumor removal, and improved survival, compared with white light surgery. These results may be translatable into clinical practice to improve surgical and patient outcomes.

Supplemental 2. RT 1x 8Gy induced immediate reduction of CD8 TILs, but did not induce significant CD8 TIL expansion at later time points.

Purpose:The use of high-dose per fraction radiotherapy delivered as stereotactic body radiotherapy is a standard of care for prostate cancer. It is hypothesized that high-dose radiotherapy may enhance or suppress tumor-reactive immunity. The objective of this study was to assess both antitumor and immunosuppressive effects induced by high-dose radiotherapy in prostate cancer coclinical models, and ultimately, to test whether a combination of radiotherapy with targeted immunotherapy can enhance antitumor immunity.Experimental Design:We studied the effects of high-dose per fraction radiotherapy with and without anti-Gr-1 using syngeneic murine allograft prostate cancer models. The dynamic change of immune populations, including tumor-infiltrating lymphocytes (TIL), T regulatory cells (Treg), and myeloid-derived suppressive cells (MDSC), was evaluated using flow cytometry and IHC.Results:Coclinical prostate cancer models demonstrated that high-dose per fraction radiotherapy induced a rapid increase of tumor-infiltrating MDSCs and a subsequent rise of CD8 TILs and circulating CD8 T effector memory cells. These radiation-induced CD8 TILs were more functionally potent than those from nonirradiated controls. While systemic depletion of MDSCs by anti-Gr-1 effectively prevented MDSC tumor infiltration, it did not enhance radiotherapy-induced antitumor immunity due to a compensatory expansion of Treg-mediated immune suppression.Conclusions:In allograft prostate cancer models, high-dose radiotherapy induced an early rise of MDSCs, followed by a transient increase of functionally active CD8 TILs. However, systemic depletion of MDSC did not augment the antitumor efficacy of high-dose radiotherapy due to a compensatory Treg response, indicating blocking both MDSCs and Tregs might be necessary to enhance radiotherapy-induced antitumor immunity.

Prior models of brain blood flow and respiratory control have not focused on instability. Time varying time delay resulting from brain blood flow changes due to carbon dioxide (CO2) and peripheral chemoreceptor gain were predicted to be important determinants of instability due to nonlinear interaction in addition to linear control loop gain. Time delay was assumed to be set by the ratio of brain arterial vascular volume and blood flow. This vascular volume was predicted to also significantly change with CO2.

A minimal model of cerebral blood flow and respiratory control was developed to describe hypocapnic and hypercapnic responses. Important nonlinear properties such as cerebral blood flow changes with arterial partial pressure of carbon dioxide ([Formula: see text]) and associated time-dependent circulatory time delays were included. It was also necessary to vary cerebral metabolic rate as a function of [Formula: see text]. The cerebral blood flow model was added to a previously developed respiratory control model to simulate central and peripheral controller dynamics for humans. Model validation was based on previously collected data. The variable time delay due to brain blood flow changes in hypercapnia was an important determinant of predicted instability due to nonlinear interaction in addition to linear loop gain considerations. Peripheral chemoreceptor gains above a critical level, but within normal limits, were necessary to produce instability. Instability was observed in recovery from hypercapnia and hypocapnia. The 20-s breath-hold test appears to be a simple test of brain blood flow-mediated instability in hypercapnia. Brain blood flow was predicted to play an important role with nonlinear properties. There is an important interaction predicted by the current model between central and peripheral control mechanisms related to instability in hypercapnia recovery. Posthyperventilation breathing pattern can also reveal instability tied to brain blood flow. Previous data collected in patients with chronic obstructive lung disease were closely fitted with the current model and instability predicted. Brain vascular volume was proposed as a potential cause of instability despite cerebral autoregulation promoting constant brain flow.

The aim of this study was to examine whether the decrease in respiratory exchange ratio (RER) during constant work-rate exercise (CWE) with 3% carbon dioxide (COinf2/inf) inhalation could be caused by the combination of the decrease in COinf2/infoutput (V̇COinf2/inf) and the increase in oxygen uptake (V̇Oinf2/inf). In addition, we investigated the effect of 3% COinf2/infinhalation on cardiac output (Q̇) during CWE.Seven males (V̇Oinf2max/inf: 44.1±6.4 mL/min/kg) carried out transitions from low-load cycling (baseline; 40w) to light intensity exercise (45% V̇Oinf2 max/inf; 89.3±12.5 W) and heavy intensity exercise (80% V̇Oinf2max/inf; 186.5±20.2 W) while inhaling normal air (Air) or an enriched COinf2/infgas (3% COinf2/inf, 21% Oinf2/inf, balance Ninf2/inf). Each exercise session was 6 min, and respiratory responses by Douglas bag technique and cardiac responses by thoracic bio-impedance method were measured during the experiment.Ventilation for 3% COinf2/infwas higher than for air through the experiment (P0.05). Steady and non-steady state RER and V̇COinf2/inffor 3% COinf2/infwere less than for air in both light and heavy intensities (P0.05), but V̇Oinf2/infand Q̇ did not differ between the two conditions.3% COinf2/infinhalation induced the decrease in RER during CWE at light and heavy intensities, which was due to the decrease in V̇COinf2/inf. The promoted ventilation with 3% COinf2/infdid not lead to the increase in V̇Oinf2/inf. Moreover, 3% COinf2/infinhalation did not affect Q̇ during CWE at light and heavy intensities.

Teaching labs at the undergraduate level poses unique challenges to a school system forced online by COVID-19. We adapted physiology laboratories typically taught in-person to an online-only format, allowing students to measure personal health data alone. Students used available technology and low-cost devices for measuring respiratory and cardiovascular parameters and analyzed the data for differences in testing conditions such as posture and exertion. Students did not physically interact, which encouraged self-directed learning but disallowed peer-to-peer education. Pre-recorded data was utilized for ECG measurements, which streamlined the process but precluded the interactive act of experimentation. The use of low-cost devices empowered and encouraged students to take ownership of their health and form important connections between their own lives and theoretical physiology. Facilitating communication and TA preparedness is key to smoothly running the virtual lab. It will be important for future virtual labs to be designed to facilitate student interaction, include hands-on experimentation, and encourage personal investigation.

This paper uses state-level data to test the Rajan hypothesis, from his book Fault Lines, that an increase in inequality can lead to a credit boom. Using dynamic heterogeneous panel estimation methods (i.e. MG, PMG, DFE), we find a significant positive long-run relationship between inequality and real estate lending across U.S. states.

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.

A nonparametric model of smooth muscle tension response to electrical stimulation was estimated using the Laguerre expansion technique of nonlinear system kernel estimation. The experimental data consisted of force responses of smooth muscle to energy-matched alternating single pulse and burst current stimuli. The burst stimuli led to at least a 10-fold increase in peak force in smooth muscle from Mytilus edulis, despite the constant energy constraint. A linear model did not fit the data. However, a second-order model fit the data accurately, so the higher-order models were not required to fit the data. Results showed that smooth muscle force response is not linearly related to the stimulation power.

Does firm diversity result in an efficient or inefficient allocation of capital? Are diversified firms “value creating” or “value destroying”? We apply a panel data model to examine the relationship between firm diversity and firm value using both COMPUSTAT and the Annual Capital Expenditure Survey (ACES) data. Our main empirical result confirms that firm diversity is negatively related to the efficiency of investment (firm value), which is consistent with the majority findings of recent studies. However, once we distinguish between capital expenditure for structures and equipment, we find that while firms do inefficiently allocate capital for equipment, they efficiently allocate capital for structures. These results suggest that when the decision has long-lasting repercussions, headquarters will, more often than not, make the correct choice.

Following a monetary tightening, bank loans to consumers decrease. This is true for both mortgage and non-mortgage loans, and it is true for a tightening by the Bank of Canada that is, and is not, a response to a tightening by the Federal Reserve System. In contrast, business loans increase following a monetary tightening. The 'per- verse' response of business loans cannot be explained by an increase in the demand for funds due to a reduction in real activity. These results are consistent with a change in bank portfolio behaviour in favour of business loans in response to a monetary tightening. Portefeuilles de prets bancaires et le mecanisme de transmission monetaire canadien. A la suite d'une restriction monetaire, les prets bancaires aux consommateurs chutent. C'est vrai tant pour les prets hypothecaires que non-hypothecaires, et c'est vrai pour une restric

In this study we present an eminent enhancement of magnetoresistance (MR) effect in FeCo alloy nanocomposite prepared by sequential implantation of 100 keV 57 Fe and 59 Co ions into Al 2 O 3 matrices. We investigated the MR effect in the granules with changing the relative amount of Fe and Co implanted to total fluences of (1.0–1.2) × 10 21 ions/m 2 and found a systematic change of MR ratio with a maximum effect around Co concentration of 25 at.%. The obtained MR ratio at room temperature and at external field H = 8.8 ×10 5 A/m is 13.2% and it is the highest value reported among the Fe, Co and FeCo granular films.

We study the portfolio behavior of bank loans following a monetary tightening and find that real estate and consumer loans sharply decrease, while commercial and industrial (C&I) loans increase. These responses are compared with responses following non-monetary shocks, which also reduce output but keep interest rates roughly unchanged. During such a “non-monetary” downturn, C&I loans sharply decrease, while real estate and consumer loans show no substantial response. These responses, together with the responses of relevant lending rates, are hard to reconcile with a decline in the supply of C&I bank loans during a monetary downturn as stressed by the bank-lending channel. Several arguments are presented explaining why the supply of C&I loans may actually increase after a monetary contraction.

We tested the effect of hypercapnic severity on plasma ammonia (Am) accumulation and respiratory exchange ratio (RER) during incremental exercise. Eight male subjects performed incremental cycle exercise to exhaustion under three conditions: breathing (1) Air, (2) 3% CO2 or (3) 6% CO2. Am in both hypercapnic conditions was lower than Air at 100% 2max O V (P

With the globalization of economic markets and the individuality of market demands, virtual enterprise is becoming an increasingly important organization since it can respond rapidly to market changes and make resource sharing more efficient among manufacturing partners. In this environment, potential partners may be located at different geographical locations and possess different core competition capabilities. Thus, how to select an optimal set of partners capable of responding to a given market opportunity—a new product or even a component, has become a challenging research topic for carrying out agile manufacturing strategy. This paper proposes a comprehensive cost function and establishes its mathematical formulation. The comprehensive cost function considers not only direct-processing cost, but also indirect-processing cost (transportation cost and time-factor cost including both earliness and tardiness). Based on the cost function, this paper presents a pragmatic approach for optimal process and partner selection in a virtual enterprise. This approach is composed of three stages: qualitative pre-qualification, quantitative evaluation, and comprehensive examination. A case study is implemented to illustrate these three stages. Compared with some traditional approaches in normal engineering activities, this approach can be expected to contribute to more efficiently reducing manufacturing cost, improving product quality, and shortening lead-time.

Transient responses of ventilation (V̇e) to limb motion can exhibit predictive characteristics. In response to a change in limb motion, a rapid change in V̇e is commonly observed with characteristics different than during a change in workload. This rapid change has been attributed to a feed-forward or adaptive response. Rate sensitivity was explored as a specific hypothesis to explain predictive V̇e responses to limb motion. A simple model assuming an additive feed-forward summation of V̇e proportional to the rate of change of limb motion was studied. This model was able to successfully account for the adaptive phase correction observed during human sinusoidal changes in limb motion. Adaptation of rate sensitivity might also explain the reduction of the fast component of V̇e responses previously reported following sudden exercise termination. Adaptation of the fast component of V̇e response could occur by reduction of rate sensitivity. Rate sensitivity of limb motion was predicted by the model to reduce the phase delay between limb motion and V̇e response without changing the steady-state response to exercise load. In this way, V̇e can respond more quickly to an exercise change without interfering with overall feedback control. The asymmetry between responses to an incremental and decremental ramp change in exercise can also be accounted for by the proposed model. Rate sensitivity leads to predicted behavior, which resembles responses observed in exercise tied to expiratory reserve volume.

A new method, round-ended tube penetration/rotation method, was developed for the continuous measurement of the viscosity from the glassy to liquid state. The reliability of the new method was tested by the measurements covering the glassy to liquid states of boron trioxide up to 1250 K and compared with previous studies. The agreement with the previous data was within errors of ±20% in glassy state and of ±10% in liquid state measurement. The viscosities of potassium meta- and di-silicates containing boron trioxide up to 50 mol%, and pseudo-binary system of potassium tetra-silicate and potassium tetra-borate were measured. The relationship between viscosity and composition is similar to that of the sodium boro-silicate system. The potassium boro-silicate system has a greater tendency to crystallization than that of the sodium boro-silicate system. Consequently, the comparison of the viscosity between both systems could only be done over a liquid temperature range.

Summary Background Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the ‘desmoglein (Dsg) compensation theory’. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti-Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti-Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus. Objectives We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme-linked immunosorbent assay. Methods To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation-immunoblotting analysis using five Dsg1/Dsg2 domain-swapped molecules. Results The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus. Conclusions These results indicate that antigenic diversity of anti-Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.

The optimization hypothesis of respiratory control during exercise is based on the minimization of a function reflecting both chemical and mechanical costs. Both additive and multiplicative controllers have been derived as optimal from similar cost functions. The purpose of the present study was to explore the uniqueness of such predictions. Various formulations of controllers compatible with isocapnia were found to yield identical costs as controllers predicted to be optimal. It was concluded that controller predictions based on optimization theory are not unique. Optimization can occur with either an additive or multiplicative controller or any combination of the two which satisfies an isocapnic constraint. A general form of a combined additive-multiplicative controller was derived which was found to be compatible with previously reported experimental data collected during combined CO2 inhalation and exercise.

This paper is the first to propose a novel quantum differential evolutionary algorithm (QDEA) based on the basic quantum-inspired evolutionary algorithm (QEA) for the non-permutation flow-shop scheduling problem (NPFSP). In this QDEA, the quantum chromosomes are encoded by using the quantum rotating angle and a simple converting mechanism for determining job sequence is proposed for the representation of NPFSP firstly. Then we merge the advantages of differential operation, local search and QEA by adopting the differential operation to perform the updating of quantum gate and the local search to perform exploitation in the promising permutative-based solutions. We adopt this approach to minimize the makespan for NPFSP and make the simulation. The comparisons with other state-of-the-art approaches based on well-known benchmarks demonstrate the effectiveness of the proposed QDEA.

Summary form only given. Low energy ion impact (with injection energy less than 50 eV or so) on the carbon-based plasma facing wall materials such as graphite of a magnetic confinement fusion device can generate a significant number of sputtered species that may enter the fusion plasma as impurities. In this work sputtering properties of graphite and amorphous carbon substrates due to hydrogen (H), deuterium (D), and tritium (T) ion bombardment at low incident energies have been studied with the use of classical molecular dynamics (MD) simulations. u The classical interatomic potentials that we have used in this work are Brenner-type multi-body potential functions with weak Van der Waals interactions. In the earlier study, we have shown that a high level of H/D/T dose accumulation on the top surface is prerequisite for the formation of relatively large-sized sputtered hydrocarbon species and also there is significant isotopic dependence of sputtering yields. The latter observation is qualitatively consistent with experimental yield data given in Ref. 5. In the present study, we have extended simulation periods for beam surface interactions in an attempt to obtain more accurate yield data for the sputtering processed discussed above. In addition, we have obtained distributions of sputtered products and their kinetic energies in these processes. Details of newly obtained data will be discussed in the presentation.

This paper examines the effectiveness of public credit guarantee programs in not only increasing the availability of loans to small and medium enterprises (SMEs), but in also improving the ex-post performance of borrowing firms. Using a unique panel data set, we identify the effects of a massive credit guarantee program implemented by the Japanese government from 1998-2001. While we do find that the availability of loans increased for program participants, when loans were provided by undercapitalized banks the increased liquidity persisted for only a few years. Further, the ex-post performance of program participants, with the exception of firms with sizable net worth, deteriorated relative to their non-participating counterparts.

Random-like fluctuations have been observed in blood flow in the microvasculature. This we term flow motion, thus distinguishing it from the closely related phenomenon, vasomotion, which refers to fluctuations in vessel diameter. This intermittent perfusion of vascular beds has been observed in skeletal muscle,1 skin,2 mesentery,3 and brain.4 These fluctuations are usually tied to spontaneously occurring rhythmic diameter variations in the feeding arterioles.5 The observations in skeletal muscle microvasculature suggest a relaxation oscillator (pacemaker) behavior with tonic modulation by perfusion pressure.6 The random nature of these fluctuations, which have readily observable periodicities, however, make response measurements difficult in terms of conventional amplitude and frequency changes. Thus, the need exists for improved methods of dealing with such responses. The question that can be asked is whether this randomness represents noise or chaos produced by a low-dimensional nonlinear system.7 The evidence given by our analysis suggests that there may be a low-order chaotic attractor. One cannot make such a conclusion with confidence, however, because the data currently available for the analysis covered only about two minute time periods. While fulfilling the requirements suggested by Grassberger and Procaccia,7 some low-frequency power in the signals would be better analyzed if the data strings were ten times as long.

Combination of congenital cardiovascular and other anomalies are often found. Combined operation is needed for some of these cases. We report 3 cases who underwent combined operations by combined team of cardiovascular and general surgical units. Case 1: A 10-month-old boy with VATER association was complicated with tetralogy of Fallot, double aortic arch and so on. He underwent division of left aortic arch for vascular ring by cardiovascular surgical unit and esophagogastrostomy for esophageal atresia by general surgical unit. Case 2: A 15-day-old girl with patent ductus arteriosus and eventration of the diaphragm underwent ligation of ductus arteriosus by cardiovascular surgical unit and plication of left diaphragm by general surgical unit. Case 3: An 8-month-old boy with tracheobronchomalacia and atrial septal defect underwent atrial septal defect (ASD) closure by cardiovascular, and extra tracheobronchial stenting on cardiopulmonary bypass by cardiovascular and general surgical unit. These 3 operations were successful, and we consider that combined operation is useful for certain surgical congenital multiple anomalies.

We have developed highly functional bioplastics (biomass-based plastics), polylactic acid composites, which improve the environmental friendliness of electronic products. A kenaf-fiber-reinforced polylactic acid has high heat resistance, high impact strength, and good moldability, and its use in PC parts and mobile phone housing has started from September 2004 and May 2006 respectively. A thermoreversibly cross-linked polylactic acid has excellent shape memory and recyclability (i.e., rewritable shape memory), and was used to create freestyle (wearable) mobile products, shape of which users can easily adjust to their own preferences.

A 1-year and 11-month-old girl with congenital mitral stenosis (MS) and patent ductus arteriosus (PDA) underwent mitral valve replacement (CarboMedics 16 mm) and ligation of PDA. Though she had suffered from severe postoperative pulmonary hypertension crisis, the inhalation of nitric oxygen (NO) with intravenous use of phosphodiesterase (PDE) III inhibitor and prostaglandin I2 (PGI2) was useful for the postoperative management. Severe pulmonary hypertension is the one of critical postoperative complications for congenital MS with PDA cases. Therefore adequate treatments, such as the combination of NO, PDE Ill inhibitor and PGI2, should be important for those cases. In our case, cardiac catetherization revealed a remaining of pulmonary hypertension under medication of beraprost sodium. Further observation should be necessary for the patient including new medicine, such as sildenafil citrate.

From 1998-2001, the Japanese government, in an effort to stimulate the flow of funds to the small business sector, implemented a massive credit guarantee program that was unprecedented in both scale and scope. Because the program was accessible by nearly every small firm we are able to clearly identify the policy effect. The program, therefore, presents a unique opportunity to determine if government intervention can improve the efficiency of credit allocation among bank-dependent small businesses. Utilizing a new panel data set of Japanese firms, which covers the implementation period of the program, we empirically test the theoretical predictions of Mankiw's (1986) adverse selection model. The model of credit markets under asymmetric information allows us to investigate whether government credit programs do more to stimulate small business investment, or serve to worsen the adverse selection problems prevalent in credit markets. We find evidence consistent with the former hypothesis. Specifically, we find that (1) program participants significantly increase their leverage, especially their use of long-term loans, and (2) with the exception of high-risk firms, become more efficient.

A 2-month-old infant was referred to our department for evaluation of a congestive heart failure. The chest X-ray showed an enlarged globular heart. Further work-up was consistent with an anomalous origin of left pulmonary artery (PA) from the ascending aorta. The patient underwent a corrective surgery using cardiopulmonary bypass. The left PA was arising 15 cm above the aortic annulus and coursed in the curved manner to the left, crossing the main PA where the media of both vessels were fused. The ligamentum arteriosus, running from the top of the main PA to the right aortic arch, was divided. The left PA was detached at its origin and anastomosed to the main PA. The anterior wall of the main PA, where the media was fused, was reinforced with polytetrafluoroethylene (PTFE) patch. An angiogram 6 months after operation showed a rapid antegrade flow to the left PA, and angiographically normal luminal contour.

A production-delivery system with volume flexibility in a single-stage supply chain is considered in this research. In this system, raw materials and/or component parts are procured from suppliers and processed into finished products, which are delivered to customers periodically at a fixed quantity with a fixed interval of time. We develop a decision-making model for optimal production rate selection. It takes into account not only raw materials' and finished goods' inventory cost but production cost as well. In this model, production rate is perceived as a decision variable and unit production cost becomes a function of production rate. A pragmatic computational approach is presented to solve the proposed model for special unit production cost functions. Finally, we conduct a numerical study to illustrate the solution.