Corporations are continually looking for new sources of innovation. Today several leading companies are beginning to find inspiration in an unexpected place: the social sector. That includes public schools, welfare-to-work programs, and the inner city. Indeed, a new paradigm for innovation is emerging: a partnership between private enterprise and public interest that produces profitable and sustainable change for both sides. In this article, the author shows how some companies are moving beyond corporate social responsibility to corporate social innovation. Traditionally, companies viewed the social sector as a dumping ground for their spare cash, obsolete equipment, and tired executives. But that mind-set hardly created lasting change. Now companies are viewing community needs as opportunities to develop ideas and demonstrate business technologies; find and serve new markets; and solve long-standing business problems. They focus on inventing sophisticated solutions through a hands-on approach. This is not charity; it is R & D, a strategic business investment. The author concedes that it isn't easy to make the new paradigm work. But she has found that successful private-public partnerships share six characteristics: a clear business agenda, strong partners committed to change, investment by both parties, rootedness in the user community, links to other organizations, and a commitment to sustain and replicate the results. Drawing on examples of successful companies such as IBM and Bell Atlantic, the author illustrates how this paradigm has produced innovations that have both business and community payoffs.
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The design of survivable mesh based communication networks has received considerable attention in recent years. One task is to route backup paths and allocate spare capacity in the network to guarantee seamless communications services survivable to a set of failure scenarios. This is a complex multi-constraint optimization problem, called the spare capacity allocation (SCA) problem. This paper unravels the SCA problem structure using a matrix-based model, and develops a fast and efficient approximation algorithm, termed successive survivable routing (SSR). First, per-flow spare capacity sharing is captured by a spare provision matrix (SPM) method. The SPM matrix has a dimension the number of failure scenarios by the number of links. It is used by each demand to route the backup path and share spare capacity with other backup paths. Next, based on a special link metric calculated from SPM, SSR iteratively routes/updates backup paths in order to minimize the cost of total spare capacity. A backup path can be further updated as long as it is not carrying any traffic. Furthermore, the SPM method and SSR algorithm are generalized from protecting all single link failures to any arbitrary link failures such as those generated by Shared Risk Link Groups or all single node failures. Numerical results comparing several SCA algorithms show that SSR has the best trade-off between solution optimality and computation speed.
Peripheral neuropathic pain is produced by multiple etiological factors that initiate a number of diverse mechanisms operating at different sites and at different times and expressed both within, and across different disease states. Unraveling the mechanisms involved requires laboratory animal models that replicate as far as possible, the different pathophysiological changes present in patients. It is unlikely that a single animal model will include the full range of neuropathic pain mechanisms. A feature of several animal models of peripheral neuropathic pain is partial denervation. In the most frequently used models a mixture of intact and injured fibers is created by loose ligation of either the whole (Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107) or a tight ligation of a part (Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990;43:205-218) of a large peripheral nerve, or a tight ligation of an entire spinal segmental nerve (Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992;50:355-363). We have developed a variant of partial denervation, the spared nerve injury model. This involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the remaining sural nerve intact. The spared nerve injury model differs from the Chung spinal segmental nerve, the Bennett chronic constriction injury and the Seltzer partial sciatic nerve injury models in that the co-mingling of distal intact axons with degenerating axons is restricted, and it permits behavioral testing of the non-injured skin territories adjacent to the denervated areas. The spared nerve injury model results in early (<24 h), prolonged (>6 months), robust (all animals are responders) behavioral modifications. The mechanical (von Frey and pinprick) sensitivity and thermal (hot and cold) responsiveness is increased in the ipsilateral sural and to a lesser extent saphenous territories, without any change in heat thermal thresholds. Crush injury of the tibial and common peroneal nerves produce similar early changes, which return, however to baseline at 7-9 weeks. The spared nerve injury model may provide, therefore, an additional resource for unraveling the mechanisms responsible for the production of neuropathic pain.
Additive Manufacturing (AM) technology has the potential to significantly improve supply chain dynamics. The purpose of this paper is to investigate the impact of AM on spare parts supply chain. Three supply chain scenarios are investigated in this paper, namely conventional supply chain, centralised AM-based supply chain and distributed AM-based supply chain. Based on system dynamics simulations, this paper specifically compares three supply chain scenarios, in terms of total variable cost and carbon emission. The results show the spare part supply chain utilising AM is indeed superior to the traditional one in sustainable performance. It is also expected that AM can facilitate the spare parts supply chain to achieve more economic benefits along with its development. To our knowledge, this paper is one of the early studies that explores the impact of AM on supply chain performance and quantitatively examines the superiority of utilising AM in spare parts supply chain. Some suggestions are also provided to help managers adopting AM in their spare parts supply chains.
Purpose The purpose of this paper is to describe and evaluate the potential approaches to introduce rapid manufacturing (RM) in the spare parts supply chain. Design/methodology/approach Alternative conceptual designs for deploying RM technology in the spare parts supply chain were proposed. The potential benefits are illustrated for the aircraft industry. The general feasibility was discussed based on literature. Findings The potential supply chain benefits in terms of simultaneously improved service and reduced inventory makes the distributed deployment of RM very interesting for spare parts supply. However, considering the trade‐offs affecting deployment it is proposed that most feasible is centralized deployment by original equipment manufacturers (OEMs), or deployment close to the point of use by generalist service providers of RM. Research limitations/implications The limited part range that is currently possible to produce using the technology means that a RM‐based service supply chain is feasible only in very particular situations. Practical implications OEMs should include the consideration of RM in their long‐term service supply chain development. Originality/value The paper identifies two distinct approaches for deploying RM in the spare parts supply chain.
This paper studies the capacity and flow assignment problem arising in the design of self-healing asynchronous transfer mode (ATM) networks using the virtual path concept. The problem is formulated here as a linear programming problem which is solved using standard methods. The objective is to minimize the spare capacity cost for the given restoration requirement. The spare cost depends on the restoration strategies used in the network. We compare several restoration strategies quantitatively in terms of spare cost, notably: global versus failure-oriented reconfiguration, path versus link restoration, and state-dependent versus state-independent restoration. The advantages and disadvantages of various restoration strategies are also highlighted. Such comparisons provide useful guidance for real network design. Further, a new heuristic algorithm based on the minimum cost route concept is developed for the design of large self-healing ATM networks using path restoration. Numerical results illustrate that the heuristic algorithm is efficient and gives near-optimal solutions for the spare capacity allocation and flow assignment for tested examples.
Inventory constraints, costs of lost production, safety and environmental objectives, strategies of maintenance adopted, logistics aspects of spare parts are some of the criteria taken into account, and spare parts classification is thus defined with respect to multiple attributes. In virtue of the large number of the potential operational characteristics to be considered, the decision diagram is integrated with a set of analytic hierarchy process models used to solve the various multi‐attribute decision sub‐problems at the different levels/nodes of the decision tree. An inventory policy matrix is defined to link the different classes of spare parts with the possible inventory management policies so as to identify the “best” control strategy for the spare stocks. The principles of the theory and an actual application in a company operating in the paper industry are reported in the paper.
With the advent of networking technologies intelligent network elements, such as the digital cross-connect system (DCS), will make it possible to dynamically reconfigure a network for restoration purposes. Both restoration control of DCSs and spare-channel design issues are presented, and how they work together so that a fast and economical SONET self-healing network is obtained. In order to achieve fast restoration, a distributed control mechanism that is applicable to both line and path restoration is proposed. The proposed method allows the shared use of spare channels for various failure scenarios, including multiple failure cases, so that the efficient use of spare channels can be achieved. A linear-programming-based scheme is proposed to obtain spare-channel assignment, where a network-flow technique is used. Through a simulation study, a fast and economical self-healing network is verified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Experimental models of peripheral nerve injury have been developed to study mechanisms of neuropathic pain. In the spared nerve injury (SNI) model in rats, the common peroneal and tibial nerves are injured, producing consistent and reproducible pain hypersensitivity in the territory of the spared sural nerve. In this study, we investigated whether SNI in mice is also a valid model system for neuropathic pain. SNI results in a significant decrease in withdrawal threshold in SNI-operated mice. The effect is very consistent between animals and persists for the four weeks of the study. We also determined the relative frequency of paw withdrawal for each of a series of 11 von Frey hairs. Analysis of response frequency using a mixed-effects model that integrates all variables (nerve injury, paw, gender, and time) shows a very stable effect of SNI over time and also reveals subtle divergences between variables, including gender-based differences in mechanical sensitivity. We tested two variants of the SNI model and found that injuring the tibial nerve alone induces mechanical hypersensitivity, while injuring the common peroneal and sural nerves together does not induce any significant increase in mechanical sensitivity in the territory of the spared tibial nerve. SNI induces a mechanical allodynia-like response in mice and we believe that our improved method of assessment and data analysis will reveal additional internal and external variability factors in models of persistent pain. Use of this model in genetically altered mice should be very effective for determining the mechanisms involved in neuropathic pain.
Yield degradation from physical failures in large memories and processor arrays is of significant concern to semiconductor manufacturers. One method of increasing the yield for iterated arrays of memory cells or processing elements is to incorporate spare rows and columns in the die or wafer. These spare rows and columns can then be programmed into the array. The authors discuss the use of CAD approaches to reconfigure such arrays. The complexity of optimal reconfiguration is shown to be NP-complete. The authors present two algorithms for spare allocation that are based on graph-theoretic analysis. The first uses a branch-and-bound approach with early screening based on bipartite graph matching. The second is an efficient polynomial time-approximation algorithm. In contrast to existing greedy and exhaustive search algorithms, these algorithms provide highly efficient and flexible reconfiguration analysis.
The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object-location recall and recognition memory in a patient, YR, who has adult-onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced-choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced-choice recognition of object-location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced-choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced-choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network-based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced-choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can also accommodate the clear impairment of forced-choice object-location recognition memory if it incorporates the view that the most complete convergence of spatial and object information, represented in different cortical regions, occurs in the hippocampus.
It is well established that the medial-temporal lobe (MTL) is critical for recognition memory. The MTL is known to be composed of distinct structures that are organized in a hierarchical manner. At present, it remains controversial whether lower structures in this hierarchy, such as perirhinal cortex, support memory functions that are distinct from those of higher structures, in particular the hippocampus. Perirhinal cortex has been proposed to play a specific role in the assessment of familiarity during recognition, which can be distinguished from the selective contributions of the hippocampus to the recollection of episodic detail. Some researchers have argued, however, that the distinction between familiarity and recollection cannot capture functional specialization within the MTL and have proposed single-process accounts. Evidence supporting the dual-process view comes from demonstrations that selective hippocampal damage can produce isolated recollection impairments. It is unclear, however, whether temporal-lobe lesions that spare the hippocampus can produce selective familiarity impairments. Without this demonstration, single-process accounts cannot be ruled out. We examined recognition memory in NB, an individual who underwent surgical resection of left anterior temporal-lobe structures for treatment of intractable epilepsy. Her resection included a large portion of perirhinal cortex but spared the hippocampus. The results of four experiments based on three different experimental procedures (remember-know paradigm, receiver operating characteristics, and response-deadline procedure) indicate that NB exhibits impaired familiarity with preserved recollection. The present findings thus provide a crucial missing piece of support for functional specialization in the MTL.
Abstract Purpose: One of the main limitations to anticancer radiotherapy lies in irreversible damage to healthy tissues located within the radiation field. “FLASH” irradiation at very high dose-rate is a new treatment modality that has been reported to specifically spare normal tissue from late radiation-induced toxicity in animal models and therefore could be a promising strategy to reduce treatment toxicity. Experimental Design: Lung responses to FLASH irradiation were investigated by qPCR, single-cell RNA sequencing (sc-RNA-Seq), and histologic methods during the acute wound healing phase as well as at late stages using C57BL/6J wild-type and Terc−/− mice exposed to bilateral thorax irradiation as well as human lung cells grown in vitro. Results: In vitro studies gave evidence of a reduced level of DNA damage and induced lethality at the advantage of FLASH. In mouse lung, sc-RNA-seq and the monitoring of proliferating cells revealed that FLASH minimized the induction of proinflammatory genes and reduced the proliferation of progenitor cells after injury. At late stages, FLASH-irradiated lungs presented less persistent DNA damage and senescent cells than after CONV exposure, suggesting a higher potential for lung regeneration with FLASH. Consistent with this hypothesis, the beneficial effect of FLASH was lost in Terc−/− mice harboring critically short telomeres and lack of telomerase activity. Conclusions: The results suggest that, compared with conventional radiotherapy, FLASH minimizes DNA damage in normal cells, spares lung progenitor cells from excessive damage, and reduces the risk of replicative senescence.
Glutathione deficiency in newborn rats, produced by administration of L-buthionine-(S,R)-sulfoximine, a transition-state inactivator of gamma-glutamylcysteine synthetase, decreases ascorbate levels of kidney, liver, brain, and lung. These tissues, especially their mitochondria, undergo severe damage and the animals die within a few days. When glutathione levels are markedly decreased, ascorbate levels decrease leading to formation of dehydroascorbate, which is degraded. Ascorbate has high antioxidant activity, but it (and other antioxidants such as alpha-tocopherol) must be maintained in reduced forms. These studies show in vivo that an important function of glutathione is to maintain tissue ascorbate. Administration of large doses of ascorbate (but not of dehydroascorbate) to buthionine sulfoximine-treated newborn rats decreases mortality, leads to normal levels of ascorbate, and spares glutathione. Newborn rats given lower doses of buthionine sulfoximine develop cataracts that, as shown previously, can be prevented by giving glutathione monoester; as found here, such cataracts can be partially prevented by administration of high doses of ascorbate or dehydroascorbate. Ascorbate spares glutathione indicating that these compounds have similar antioxidant actions. Ascorbate may have reductive functions that are not efficiently performed by glutathione. Although glutathione normally functions to maintain ascorbate, alpha-tocopherol, and other cellular components in reduced states, ascorbate can serve as an essential antioxidant in the presence of severe glutathione deficiency.
Accurate predictions of equipment failure times are necessary to improve replacement and spare parts inventory decisions. Most of the existing decision models focus on using population-specific reliability characteristics, such as failure time distributions, to develop decision-making strategies. Since these distributions are unaffected by the underlying physical degradation processes, they do not distinguish between the different degradation characteristics of individual components of the population. This results in less accurate failure predictability and hence less accurate replacement and inventory decisions. In this paper, we develop a sensor-driven decision model for component replacement and spare parts inventory. We integrate a degradation modeling framework for computing remaining life distributions using condition-based in situ sensor data with existing replacement and inventory decision models. This enables the dynamic updating of replacement and inventory decisions based on the physical condition of the equipment.
Abstract A modern military organization like the UK's Royal Air Force is dependent on readily available spare parts for in-service aircraft in order to maximize operational capability. A large proportion of spare parts are known to have an intermittent or slow-moving demand pattern, presenting particular problems as far as forecasting and inventory control are concerned. In this paper, we use extensive demand and replenishment lead-time data to assess the practical value of forecasting models put forward in the literature for addressing these problems. We use an analytical method for classifying the consumable inventory into smooth, irregular, slow-moving and intermittent demand patterns. Recent forecasting developments are compared against more commonly used methods across the identified demand patterns. One recently developed method, a modification to Croston's method referred to as the approximation method, is observed to provide significant reductions in the value of the stock-holdings required to attain a specified service level for all demand patterns.
INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and for predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells, was described as a marker of cancer-initiating cells in different tumor types. Here, we report that a CD133+, epithelial-specific antigen-positive (CD133+ESA+) population is increased in primary nonsmall cell lung cancer (NSCLC) compared with normal lung tissue and has higher tumorigenic potential in SCID mice and expression of genes involved in stemness, adhesion, motility, and drug efflux than the CD133(-) counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction both after acute cytotoxic exposure and in cells with stable cisplatin-resistant phenotype. Subpopulations of CD133+ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts established from primary tumors. A tendency toward shorter progression-free survival was observed in CD133+ NSCLC patients treated with platinum-containing regimens. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and the definition of predictive factors in clinical management of this lethal disease.
Blocking the CD28-B7 T cell costimulatory pathway with the fusion protein CTLA4Ig inhibits alloimmune responses in vitro and in vivo and induces tolerance to cardiac allografts in mice and rats, but the mechanisms mediating the tolerant state in vivo are unknown. Here, we report the effects and potential mechanisms of CTLA4Ig in the rat renal allograft model. LEW rats were nephrectomized and received renal allografts from major histocompatibility complex-incompatible WF rats. While all untreated and control immunoglobulin (Ig)-treated animals acutely rejected their allografts and died, 86% of rats that received a single injection of CTLA4Ig on day 2 after transplantation had prolonged survival (> 60-100 days) with preserved renal function. By contrast, only 29% of animals that received CTLA4Ig on the day of engraftment had prolonged survival. Long-term survivors (> 100 days) exhibited donor-specific tolerance, accepting donor-matched WF but acutely rejecting third-party BN cardiac allografts. Immunohistological analysis of grafts sampled at 1 week after transplantation showed that both control and CTLA4Ig-treated animals had mononuclear cell infiltrates, with a higher percentage of CD4+ cells in the CTLA4Ig-treated group. However, while this was associated with vasculitis and tubulitis in control grafts, there was no evidence of tissue injury in CTLA4Ig-treated animals. The immune response leading to graft rejection in control animals was characterized by expression of the T helper (Th) type 1 cytokines interleukin (IL)-2 and interferon-gamma. In contrast, the persistent CD4+ infiltrate without graft rejection in CTLA4Ig-treated animals was associated with increased staining for the Th2-related cytokines IL-4 and IL-10. Furthermore, grafts from CTLA4Ig-treated animals had marked upregulation of intragraft staining for IgG1, but not IgG2a or IgG2b. Administration of rIL-2 to CTLA4Ig-treated animals restored allograft rejection in 50% of animals tested. These results confirm that blockade of the CD28-B7 pathway after alloantigenic challenge induces donor-specific acceptance of vascularized organ allografts, and indicates in this model that CTLA4Ig inhibits Th1 but spares Th2 cytokines in vivo.