This thesis in the field of inventory management for deteriorating items studies the effects of deterioration on optimal policies in inventory and production-inventory models. Four different models are developed and analysed to address some of the gaps identified in this part of the inventory management literature. The first two models have been studied adopting the classic approach towards inventory modelling, where the holding cost is assumed to be proportional to a known exogenous unit holding cost parameter. Taking this approach, first a two-echelon (single-buyer, single-supplier) model is investigated in which the capacity is considered to be limited. In this model also the exact inventory level over time of the supplier is obtained whereas the literature to date has only considered the average inventory level. As the analysis shows, this results in a complex model, and therefore a heuristic is developed. In the second model, a single supplier, multiple buyers system is developed where there is a (in)finite production rate. It has been identified that the literature fails to calculate accurately the average inventory level of the supplier in situations where the production rate is finite. In this model this issue has been addressed, and further analysis reveals the significance of the more accurate modelling approach developed. The literature evaluates inventory models in different ways in terms of objective function. A body of research is identified in the literature that assumes an equivalence between profit maximisation and cost minimisation, and it often seems logical to discard revenues and minimise the cost function. This equivalence, however, is not always easily established when the objective function is to maximise the Net Present Value (NPV) of the profit function. In the third model of this thesis, this equivalence is analysed in detail, and it is shown that taking a cost minimisation model instead of a profit maximisation objective in some cases should be done cautiously and in the best case only adopted after establishing the relevant equivalence conditions using NPV Equivalence Analysis (NPVEA). Finally, in a fourth model a two-echelon supply chain with capacity constrains is developed using the NPV criterion. In this model a modification in the inventory level is suggested which makes the model more practical compared to the existing models in cases that the customers are serviced from the own warehouse.


Neuronal degeneration has been shown to be involved in various neurological disorders. Growth/trophic factors and their receptors are known to be important for the regeneration and survival of neurons. We report here the molecular cloning of a receptor‐like protein tyrosine kinase, bsk, (for brain specific kinase). Bsk is highly related to the eph/elk receptor like kinase family members. Northern blot analysis shows that is is expressed specifically in the brain, with no expression detected in adult heart, spleen, lung, liver, skeletal muscle, and kidney. In situ hybridization analysis of adult mouse brain sections indicates that bsk is expressed at high levels in the hippocampus, tenia tects, indusium griseum, and the piriform cortex, major components of the limbic system that are important for learning and memory. In addition, elevated levels of expression are found in other areas of the limbic system such as the amygdala, medial septum, and nucleus of the diagonal band, and in the olfactory bulb, which has close connections to the limbic system. The highest level of expression is found in the CA3 region of the hippocampus and the pyramidal cell layer of the piriform cortex. In 16.5 day mouse embryos, bsk is expressed predominantly in the primordial cortex of the telencephalon. An antibody against a C‐terminal peptide of bsk recognized a 105 kD protein in the 16.5 day embryonic head extract. Our analysis shows that bsk is a growth factor receptor‐like protein tyrosine kinase and that its greatest expression in the adult brain is associated with components of the limbic system. © 1994 Wiley‐Liss, Inc.


Details regarding claims of rubella occurred in Lombardia (Italy) have been collected by the AA., in force at the Regional Health Services. The results have been also compared with the claimed cases of abortus and of malformed newborn. The first results of voluntary vaccination, promoted by the Regional Services, both on children of the 5th Classes of Primary School and on women more exposed to risks provoked by rubella infections are also reported.


The approach to the radiographic diagnosis of bone tumors consists of analyzing the lesion in an organized fashion, with attention to the specific radiographic features of tumor location, margins, and zone of transition; periosteal reaction; mineralization; size and number of lesions; and presence of a soft-tissue component. Patient age is also an important clinical factor in the diagnosis of bone tumors, because various lesions have predilections for specific age groups.


In 1975, the mayor of Ankara requested Soviet assistance to build a public transportation system and affordable housing in the Turkish capital. This article uses Vedat Dalokay's appeal as a window into international development politics during a transformative decade. The 1970s saw growing leftism in Turkey, and Dalokay hoped that progressive urban planning would solidify voting trends among rural-to-urban migrants. He sought to introduce a new ideological element into Soviet–Turkish exchange, but politicians and academics in Moscow dismissed Dalokay's class-oriented projects. Instead, they increased their investments in the steel mills and electricity plants that were hallmarks of Soviet economic exchanges with the Third World. Whereas Dalokay's aspirations emerged from a Turkish intellectual climate that was being reshaped by dependency theory and by disillusionment in the possibilities for growth within boundaries defined by the political borders of nation-states, Soviet economists and bureaucrats remained wedded to the idea of development defined in terms of the territorial economy. The Ankara municipality eventually turned to Western Europe, but the Turkish government continued to negotiate gas pipelines and nuclear power plants with the Soviet and post-Soviet Russian governments. This article explores the ideological assumptions that have shaped economic exchange across the Black Sea.


We compare four explanations for the value of diplomas, each of which has implications for unemployment and wage variation amongst graduates, most of which have not previously been tested for when seeking to explain the effects of diplomas. We test for these implications using a refined econometric framework, exploiting idiosyncrasies in Mexican labour market and educational institutions. Premiums in Mexico appear to result from diplomas tied to jobs with downwards rigid wages – an uncommon but simple explanation. The standard explanations, including screening, are not suggested by Mexican data. Our results illuminate how labour markets segmented by diplomas clear. This depends upon the nature of the labour market rigidities exactly as predicted by neoclassical theory.


Author(s): Wu, Yuan-Yun | Advisor(s): Lee, Chin C. | Abstract: In this dissertation, fluxless silver (Ag)-indium (In) binary system bonding and Ag solid-state bonding are used between different bonded pairs which have large thermal expansion coefficient (CTE) mismatch and flip-chip interconnect bonding application. In contrast to the conventional soldering process, fluxless bonding technique eliminates contamination and reliability problems caused by flux to fabricate high quality joints. Due to large CTE mismatch, high quality joints are important to manage the shear strain which develops in the bonded objects. Besides, the resulting Ag and Ag-In joints have relative high melting and operating temperature which can be utilized in high temperature packages. There are two section are reported. In the first section, the reactions of Ag-In binary system are presented. In the second section, the high melting temperature, thermal and electrical conductivity joint materials bonding by either Ag-In binary system bonding or solid-state bonding processes for different bonded pairs and flip-chip application are designed, developed, and reported. Our group have studied Ag-In system for several years and developed the bonding processes successfully. However, the detailed reactions of Ag and In were seldom studied. To design a proper bonding structure, it is necessary to understand the reaction between Ag and In. The systematic experiments were performed to investigate these reactions. A 40 um Ag layer was electroplated on copper (Cu) substrates, followed by indium layers of 1, 3, 5, 10, and 15 um, respectively. The samples were annealed at 180 °C in 0.1 torr vacuum. For samples with In thickness less than 5 um, the joint compositions are Ag2In only (1 um) or AgIn2, Ag2In, and Ag solid solution (Ag) after annealing. No indium is identified. For 10 and 15 um thick In samples, In covers almost over the entire sample surface after annealing. Later, an Ag layer was annealed at 450 °C for 3 hours to grow Ag grains, followed by plating 10 um In and annealing at 180 °C. By annealing Ag before plating In, more In is kept in the structure during annealing at 180 °C. Based on above results, for those designs with In thinner than 5 um, the Ag layer needs to be annealed, prior to In plating in order to make a successful bonding. In this section, we further studied the Ag-In bonding and solid-state bonding for different bonded pairs and flip-chip application. For the silicon (Si) and aluminum (Al) pair, Al has been used as the material for interconnect pads on the ICs. However, its high CTE (23 × 10-6/°C) and non-solderable property limit its applications in electronic products. To overcome these problems, a fluxless Ag-In bonding was developed. Al was deposited Cr/Cu layer on the surface by E-beam evaporator to make it solderable. 15 um of Ag and 8 um of In were sequentially plated on the Al substrates and 15 um of Ag was on Si chips with Cr/Au coating layer. The bonding was performed at 180 °C in 0.1 torr vacuum. The joint consists of Ag/(Ag)/Ag2In/(Ag)/Ag. The joint can achieve a solidus temperature of beyond 600 °C. From shear test results, the shear strengths far exceed the requirement in MIL-STD-883H. Al is not considered as a favorable substrate material because it is not solderable and has a high CTE. The new method presented in this thesis seems to have surmounted these two challenges. Since Ag2In is weak inside the joint in Ag-In system, an annealed process was used to convert the joints into Ag solid solution (Ag) to increase the joint strength and ductility. Two copper (Cu) substrates were bonded at 180 °C without flux. Bonding samples were annealed at 200 °C for 1,000 hours (first design) and at 250 °C for 350 hours (second design), respectively. Scanning electron microscope with energy dispersive X-ray (EDX) analysis results indicate that the joint of the first design is an alloy of mostly (Ag) with micron-size Ag2In and Ag3In regions, and that of second design has converted to a single (Ag) phase. Shear test results show that the breaking forces far exceed the requirement in MIL-STD-883H. The joint solidus temperatures are 600 °C and 800 °C for the first and second designs, respectively. The research results have shown that high-strength and high temperature joints can be manufactured using fluxless low temperature processes with the Ag-In system and are valuable in developing high temperature package. For real applications, a serious concern is the long-term reliability of the joints under thermal stress caused by CTE mismatch between the chip and the package. Thereby, the reliability of Ag-In joints in thermal cycling (TC) environment is assessed. Si chips and Cu substrates were bonded at 180 °C without flux, and then annealed at 250 °C to convert the joint into an alloy of intermetallic grains and (Ag). Si-Cu pair is chosen because of the large CTE mismatch. Two TC tests were performed. 10 samples were examined from -40 °C to 85 °C for 100 cycles first and -40 °C to 200 °C for 5,000 cycles later. Seven of ten samples survived beyond 5,000 cycles. Based upon these results, the Ag-In joints not only have high melting temperature but also can survive harsh TC environment. To further investigate other alternative bonding method, the solid-state atomic bonding technique is introduced. High quality joints are crucial to bonding materials with CTE mismatch since shear stress develops in the bonded pair. Since stress concentrated at the voids in these joint, the breakage probability could increase. In addition, intermetallic compound (IMC) formation between the solder and under bump metallurgy (UBM) is essential for interconnect joint formation in the conventional soldering process. However, the interface between the IMC and solder is shown to be the weakest interface that tends to break first during thermal cycling and drop tests. Thus, we developed a solid-state bonding process along with ductile joint materials that no molten phase was included. Thus, the IMC and its related issues are eliminated. In the first bonding experiment, 10 um Ag layer with cavities were produced on the Si chips with Cr/Au coating layer and then bonded to the Cu substrates at 300 °C with 1,000 psi (6.9 MPa) static pressure in vacuum. Due to cavities, the bonding pressure can be reduced to 600 psi (4.1 MPa). No underfill or flux is needed. From cross-section SEM images, Ag joints are well bonded between Si chips and Cu substrates. The shear test results show that bonding strengths pass the MIL-STD-883H, except one sample. It eliminates a concern from the bonding strength for practical applications. Due to the miniaturization of large-scale-integration of circuits on Si chip technology, the joint size and the pitch of the flip-chip joints have to be scaled down. As the joint shrinks, reliability issues and manufacturing difficulties emerge. One of these difficulties is elevated shear strain due to the increase of the intermetallic compound (IMC) layer ratio. Therefore, we demonstrated the Ag flip-chip interconnect process using solid-state bonding at 250 °C with a static pressure 800 psi in vacuum. Each Si chip has an array of 50 × 50 × 13 Ag flip-chip joints with 20 um in pitch and 10 um joint in diameter on Si chip. No flux or underfill is needed. The cross-section SEM image shows that the Ag flip-chip joints were well bonded to the Cu substrate without cracks. Despite a large CTE mismatch between Si and Cu, no joint breakage is observed. The ductile Ag joint well manage the stress induced by significant CTE mismatch. The melting temperature of joints is 962 °C. Thus, high operating temperature device such as 200-450 °C becomes possible. To further evaluate this, a pull-off-test was performed. The breaking force was 1.5 times larger than the MIL-STD-883H criterion. There are several advantages to this solid-state Ag flip-chip bonding technology: high electrical and thermal conductivities, no IMCs and their related issues, a complete lack of flux, high ductility for managing CTE mismatch between chips and packages, high operating temperature, and possibility for a high aspect ratio of the interconnect. To figure out the stress-strain of Ag and (Ag) at room temperature and elevated temperature, a typical ingot with 9.5 mm in diameter and 60 mm in length was fabricated. The main ingots were machined into ASTM tensile test samples by EDM. The stress-strain curves of Ag were measured at room temperature, at 221 °C (Th = 0.4), and at 350 °C (Th = 0.5), respectively, where Th is the homologous temperature. For Ag ingot, at room temperature, the yield strength (YS) ranges from 51 to 106 MPa and ultimate tensile strength (UTS) is from 138 to 208 MPa which are comparable with the published data but the elongation (0.27 - 0.49) is about twice of the published value. At higher temperatures, the YS and UTS decrease but elongation varies little. Silver solid solution with 20 at. % In ((Ag)-In20) samples were also measured at room temperature, at 156 °C (Th = 0.4), and at 265 °C (Th = 0.5), respectively. (Ag)-In20 test samples have better results than pure Ag test sample. The YS is 14 MPa which is smaller than pure Ag test sample but UTS (308 MPa) and elongation (0.73) are 1.5 times of pure Ag sample.


The pathology of calves that died from experimental water intoxication was investigated. Oedema of the brain and urinary bladder, and renal damage were significant pathological findings in these calves. The findings were attributed to positive water balance in calves suffering from water intoxication.


With IoT, billions of physical sensors/actuators nodes will be connected to the internet. Due to their massive quantity, the only sustainable way to power them is through environmental energy harvesting (EH). The major subsystems of an indoor/outdoor lighting EH system are the PV cell to harvest light energy, and energy storage device to store the harvested energy.
In this project, the energy storage and wireless sensor node were worked on primarily. Energy storage devices that were used to power up the wireless sensor node include NiMH cells. The wireless sensor node consisted of a temperature and humidity sensor which then transmitted data via radio modules.
To obtain the battery characteristics in the energy harvesting system, some parameters had to be acquired. These included the series resistance, parallel resistance, and parallel capacitance. This was done by pulse charging a battery at 1C for 1 minute. Then, the parameters were obtained using several formulas.
The data obtained from the discharge experiment was also input into a simulation model. From there, comparisons between experimental and simulated data were made to verify whether the modelling of the battery is within the boundaries or not.


in any of the healthy districts of the colony or far distant from human habitations, nor have I yet found them in rice fields, in large pools of water, in rapidly-running streams, in pools with sandy bottoms, in wells, old broken pottery, tubs, pans, etc., as in the case of Culex, which may be found in almost anything which contains water. In contradistinction to the Anopheles, water weed does not seem to be necessary to the existence of the Culex larva, they being often found in pools, etc., from which it is entirely absent; a further distinction between the two species being that the former appears to be much more delicate than the latter. It is not necessary here to describe the Anopheles larva or mosquito, they being so entirely different from the other species as to be easily recognised after having been once seen. Having satisfied myself as to the existence of the Anopheles in the colony, and having given a brief description of its habitat, etc., I will now pass on to the possibilities of its extirpation from the island. With this object in view I have been teating the effects of various insecticides. I found that kerosene used as described by the African Commission was very effective in still pools, or in those which were temporarily stagnant; gas tar also proved to be very useful, but in my opinion Jeyes' fiuid is the best of those which I have tried up to the present. So far as my experiments have gone, I find that one part of Jeyes' fluid to io,ooo of water kills both Anophekes and Culex larvse in a few hours, very much weaker solutions destroying them after a longer interval. Permanganate of potash appears to be of very little use. In a solution of I to i,200 of water, equal to I in 5 of Condy's fluid, the larvae lived for twenty-four hours, and were as lively as ever at the end of that time; while in a solution of I to 5oo, equal to nearly I in 2 of Condy's fluid, they lived for four hours without there being any appreciable effect upon them, and even after twenty-four hours more than half of them were alive. Hence, by treating all Anopheles resorts frequently with Jeyes' flaid, kerosene, or gas tar during the whole of the dry season, when such pools are comparatively scarce, and by paying particular attention to surface drainage in malarial districts, much might be done towards effecting their partial, if not total, extermination.


Toxic shock syndrome (TSS) is caused by toxic shock syndrome toxin 1 or enterotoxins secreted by Staphylococcus aureus. Lipopolysaccharide (LPS) has also been shown to play a major role in the development of sepsis. Staphylococcal superantigens and LPS operate synergistically in conditioning cytokine release and lethal shock in mice. An 80‐year‐old woman was admitted because of a 20% mixed‐depth flame burn. Despite two excisions and grafts, necrotic ulcers with methicillin‐resistant Staphylococcus aureus (MRSA) colonization remained. On the 7th day after the operation, she developed shock with an erythematous rash. Blood examination revealed evidence of disseminated intravascular coagulation, and liver and renal dysfunction. A blood culture revealed a staphylococcal enterotoxin B (SEB)‐producing strain of MRSA and Klebsiella pneumoniae. The septic symptoms were prolonged, but the condition gradually improved with extensive treatment. T‐cell receptor analysis demonstrated a marked accumulation of SEB‐mediated Vβ T cells. Stimulation of peripheral blood mononuclear cells in the recovery phase with SEB and LPS induced additive effects on tumor necrosis factor‐α, interferon‐γ, and interleukin‐6 production. Although the present case did not fulfill the clinical criteria for TSS, the additive effects of SEB and LPS might have caused the severe septic shock.


Supramolecular strategies, based on hydrogen bonds and ionic interactions, were investigated as tools for the recovery and recycling of homogeneous transition-metal catalysts by using reverse-flow adsorption (RFA) technology. The association (in solution) and adsorption (on support) of new functionalized host materials and phosphine guest ligands, functionalized with the complementary binding motifs, were fine-tuned for the application of these materials in a RFA reactor. The RFA technology for process-integrated recycling of homogeneous catalysts using these tailor-made phosphine ligands and silica-supported host materials resulted in a stable, semicontinuous catalytic system. Rhodium-catalyzed asymmetric hydrogenation of methyl acetamidoacrylate and asymmetric hydrosilylation of acetophenone were studied as test reactions. Depending on the catalytic process the metal complex could be recycled several times without significant loss in conversion.


The geochemical evolution of metamorphic rocks during subduction‐related metamorphism is described on the basis of multivariate statistical analyses. The studied data set comprises a series of mapped metamorphic rocks collected from the Sanbagawa metamorphic belt in central Shikoku, Japan, where metamorphic conditions range from the pumpellyite–actinolite to epidote–amphibolite facies. Recent progress in computational and information science provides a number of algorithms capable of revealing structures in large data sets. This study applies k‐means cluster analysis (KCA) and non‐negative matrix factorization (NMF) to a series of metapelites, which is the main lithotype of the Sanbagawa metamorphic belt. KCA describes the structures of the high‐dimensional data, while NMF provides end‐member decomposition which can be useful for evaluating the spatial distribution of continuous compositional trends. The analysed data set, derived from previously published work, contains 296 samples for which 14 elements (Si, Ti, Al, Fe, Mn, Mg, Ca, Na, K, P, Rb, Sr, Zr and Ba) have been analysed. The KCA and NMF analyses indicate five clusters and four end‐members, respectively, successfully explaining compositional variations within the data set. KCA indicates that the chemical compositions of metapelite samples from the western (Besshi) part of the sampled area differ significantly from those in the east (Asemigawa). In the west, clusters show a good correlation with the metamorphic grade. With increasing metamorphic grade, there are decreases in SiO2 and Na2O and increases in other components. However, the compositional change with metamorphic grade is less obvious in the eastern area. End‐member decomposition using NMF revealed that the evolutional change of whole‐rock composition, as correlated with metamorphic grade, approximates a stoichiometric increase of a garnet‐like component in the whole‐rock composition, possibly due to the precipitation of garnet and effusion of other components during progressive dehydration. Thermodynamic modelling of the evolution of the whole‐rock composition yielded the following results: (1) the whole‐rock composition at lower metamorphic grade favours the preferential crystallization of garnet under the conditions of the garnet zone, with biotite becoming stable together with garnet in higher‐grade rock compositions under the same P–T conditions; (2) with higher‐grade whole‐rock compositions, more H2O is retained. These results provide insight into the mechanism suppressing dehydration under high‐P metamorphic conditions. This mechanism should be considered in forward modelling of the fluid cycle in subduction zones, although such a quantitative model has yet to be developed.


The purpose of this study is to address the lack of research into the challenges and issues recoupled parents face when raising their step/biological children with autism spectrum disorder (ASD) together in a stepfamily environment. Data shows clinicians, community support services, and policy makers are recognising that stepfamilies are the fastest growing family form to date and hypothesising stepfamilies will become the norm as the most prominent family form in most western countries. Ongoing research recognises the importance of understanding parents' experiences and perspectives of having a child with ASD, and resourcing and managing their child's everyday needs, behaviour and necessary treatments. Research exploring the parents' journey of supporting a child with ASD will benefit families and other relevant formal and informal supports involved with that child. Stepfamilies are distinctly different to the nuclear family in design, origin and function. The researcher, through a small-scale qualitative case study, interviewed two recoupled parents to gain insights from their own personal and stepfamily experiences. This study has substantiated the existing research and highlighted other specific challenges and issues recoupled parents of children with ASD face. The researcher uses the term step/biological children throughout this article in recognition that the child/children is/are connected to one parent as a blood child and the stepparent through the biological parents' choice in re-partnering. The outcome of this research indicates the need for recoupled parents to have a forum to express their subjective experiences in raising children with ASD. The interviewees articulated the need for further understanding from professional and informal supports when working with children and parents in a stepfamily form.


Conventionally, the uncertainties of channel coefficients are neglected, that is the estimated values of channel coefficients are taken as the true values in the stage of data detection. In the communications community, it is still an open question how to take into account the channel uncertainty for data detection/decoding, especially in a low-complexity manner. In this paper, we propose a low-complexity receiver algorithm which utilizes soft channel information. Channel coefficients are treated as variables and estimated in an element-wise manner. Their uncertainties are represented by the variances. Instead of performing channel estimation and data detection in a separate manner, this algorithm does everything in one stage, i.e., channel estimation and data detection/decoding are carried out simultaneously over a general factor graph. The feasibility of this algorithm is verified by means of Monte-Carlo simulations both in bit error ratio (BER) and channel estimation mean squared error (MSE).


The increasing availability of dual-energy CT (DECT) has set the stage for an exciting era in CT technology. This technique is extensively used throughout the world with numerous centres working on the applications of DECT in various radiology subspeciality areas. DECT provides many advantages over the conventional single-energy scan. Instead of a single set of images, radiologists have access to multiple sets of images from a single acquisition. The DECT workstation enables the reader to generate images, according to the clinical setting, in order to answer a specific clinical question. Radiologists should be aware of the basic concepts of DECT and the usefulness of each image data set. This article aimed to describe the basic principles, techniques and applications of DECT in the imaging of salivary gland lesions. The specific roles of each image data set, in the context of salivary gland lesions, are also discussed.


The article describes a case of successful treatment of a child not elder than 1 year old with a gangrene in the right upper lobe of the lung against the background of its cystic adenomatoid malformation. The disease manifested as pneumonia. The diagnosis was confirmed following multispiral computed tomography. The first stage of surgery was drainage of the pleural cavity. Thoracotomy and upper lobe lobectomy were done after a child's condition had stabilized. Gangrene in the cystic and adenomatoid piece of the lobe was confirmed macroscopically and histologically.


In recent decades political and economic interest has focused on a phenomenon known as the 'growth of government', a euphemism for rising public expenditure. Studies that have focused on the process are broadly classified into three distinct areas those that highlight the phenomenon (Saunders and Klau, 1985); those that identify the contributory factors (Henrekson, 1990) and those that embrace both approaches (Lybeck and Henrekson, 1988; Gemmell, 1993). Whilst such studies highlight the differing rates of growth in public expenditure across the industrialised nations of the world, there are a number of common strands. For example, the 1950s and 1960s were generally viewed as a period of stable growth, whereas in the 1970s, especially since the first oil crises of 1973, there was dramatic growth due to rising levels of unemployment and expansionary fiscal policies. However, the 1980s and 1990s represent a sea change in the pattern of public expenditure growth. During this period the consensus has been that the size of the public sector has exceeded the willingness of the voter-tax-payer to finance it. As a result, there is greater pressure on fiscal budgets and policies have been introduced to reduce the role of the public sector generally and public expenditure in particular.


This paper discusses the methodology in developing a 3D CAD system for injection mold. There are hundreds of parts in a set of mold, these parts can be classified and managed by an assembly method. The assembly tree structure can be looked upon as a reverse tree, each branch represents a sub-assembly tree structure, and leaves are part files. The parts are created by parametric geometrical model, parameters are used to control part size. A linkage between geometrical model and part database was built up to load the standard parts automatically. Associations are created among these parts by referring parameters with each other. A version management method is discussed to keep design status and restore to previous design as necessary. Mold design specification functions such as parting, cooling, mold base, insert creation are also provided to designers. A knowledge-based 3D CAD system is currently being used in the local mold design and manufacturing companies.


Rab GTPases (Rabs) are small proteins that play crucial roles in vesicle transport and membrane trafficking. Owing to their widespread functions in several steps of vesicle trafficking, Rabs have been implicated in the pathogenesis of several disorders, including cancer, diabetes, and multiple neurodegenerative diseases. As treatments for neurodegenerative conditions are currently rather limited, the identification and validation of novel therapeutic targets, such as Rabs, is of great importance. This review summarises proof-of-concept studies, demonstrating that modulation of Rab GTPases in the context of Alzheimer's disease (AD) can ameliorate disease-related phenotypes, and provides an overview of the current state of the art for the pharmacological targeting of Rabs. Finally, we also discuss the barriers and challenges of therapeutically targeting these small proteins in humans, especially in the context of AD.


OBJECTIVE
To investigate the incidence of hypothalamus-pituitary-gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery.

METHODS
A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006-2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups.

RESULTS
Of 127 suprasellar GCT patients, 75 met the follow-up criteria, and 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% confidence interval (CI) 2.2-25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI 1.4-17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI 1.5-20.7, P = 0.009) were risk factors for noninitiation/recovery.

CONCLUSIONS
Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.


We have obtained new observations of the partial Lyman limit absorber at \zabs$=0.93$ towards quasar PG~1206+459, and revisit its chemical and physical conditions. The absorber, with $ N(HI) \sim 10^{17.0}$ ~\sqcm\ and absorption lines spread over $\gtrsim$1000~\kms\ in velocity, is one of the strongest known OVI absorbers at $\log N(OVI)=$15.54$\pm$0.17. Our analysis makes use of the previously known low-(e.g. \MgII), intermediate-(e.g. SiIV), and high-ionization (e.g., CIV, NV, NeVIII) metal lines along with new $HST/$COS observations that cover OVI, and an $HST/$ACS image of the quasar field. Consistent with previous studies, we find that the absorber has a multiphase structure. The low-ionization phase arises from gas with a density of $\log (n_{\rm H}/\rm cm^{-3})\sim-2.5$ and a solar to super-solar metallicity. The high-ionization phase stems from gas with a significantly lower density, i.e. $\log (n_{\rm H}/\rm cm^{-3}) \sim-3.8$, and a near-solar to solar metallicity. The high-ionization phase accounts for all of the absorption seen in CIV, NV, and OVI. We find the the detected \NeVIII, reported by \cite{Tripp2011}, is best explained as originating in a stand-alone collisionally ionized phase at $T\sim10^{5.85}~\rm K$, except in one component in which both OVI and NeVIII can be produced via photoionization. We demonstrate that such strong OVI absorption can easily arise from photoionization at $z\gtrsim1$, but that, due to the decreasing extragalactic UV background radiation, only collisional ionization can produce large OVI features at $z\sim0$. The azimuthal angle of $\sim88$\degree\ of the disk of the nearest ($\rm 68~kpc$) luminous ($1.3L_*$) galaxy at $z_{\rm gal}=0.9289$, which shows signatures of recent merger, suggests that the bulk of the absorption arises from metal enriched outflows.


A design is proposed for a mechanical device made of a nanoscale pinion sandwiched without contact between two racks that exert opposing forces rooted in the quantum fluctuations of the electromagnetic field via the lateral Casimir force. The built-in frustration in the design of the system helps it to react dramatically to minute changes in the geometrical features, which suggests that it could act as a good sensor. The noncontact nature of this device could help solve the infamous wear problem in nanoscale mechanical devices.


This paper reports on the metacognitive listening strategies used by second language successful learners when listening to a text in English. It is part of a larger study where 82 students were surveyed in regards to metacognitive listening strategies using the Metacognitive Awareness Listening Questionnaire (MALQ). Three successful listeners from among the 82 students volunteered to take part in the verbal reports (think-aloud protocols) in an attempt to uncover the metacognitive listening strategies this group of learners uses. The research question I sought to answer was: What are the metacognitive strategies that successful level four female Saudi students at the College of Languages and Translation at King Saud University report using while listening to a text in English? Results indicated that when listening in English, this group of learners use problem-solving and directed attention strategies more often than other types of metacognitive strategies.


Psidium quajava has for long been employed in the management of many diseases in Kenya, including diabetes mellitus. However, the use of this plant extract lacks scientific validation in regard to its efficacy. This study aimed at investigating in vivo antidiabetic activity of aqueous extract of Psidium quajava in alloxanized diabetic mice. Antidiabetic property was assessed through oral and intraperitoneal administration of aqueous plants extract at doses of 50, 100, 200 and 300mg/kg body weight and profiling the levels of blood glucose after 0, 1, 2, 3, 4, 6 and 24 hours using a glucometer. The mineral composition of the aqueous plant extract was assayed using Total Reflection X-ray Fluorescence system (TRXF), while the different types of secondary metabolites were assessed using standard procedures. The aqueous plant extract exhibited a dose dependent hypoglycemic activity in alloxanized diabetic mice. The studied plant extract contained alkaloids, flavonoids, saponins, tannins, and total phenols at varying concentration. The mineral profile demonstrated the presence of detectable levels of K, Ca, Ti, V, Mn, Fe, Ni, Cu, Zn and As. The plant's aqueous extract was effective in lowering blood glucose levels.


The FACCE MACSUR kickoff meeting took place 15-16 October 2012 in Berlin, Germany. The date for the meeting was moved from July to October to accommodate the participation of most institutions involved in MACSUR in a sufficiently large meeting place. One hundred and forty-five persons participated in the event. The meeting was organized as a workshop to allow for expanded time for interaction among the participants of the 73 involved institutions. The keynote lectures by Tim Benton (Global Food Security and University of Leeds) and Tim Carter (Finnish Environment Institute – SYKE) set the background by describing the need for assessing future impacts on food security and how to deal with the uncertainty associated with data, models, and projections. In parallel sessions participants discussed the organization of the work in the project and in each Theme, common approaches to answering the questions, selection of scenarios, involvement of stakeholders, and how the results will be presented. The results of the four cross-cutting workshops are documented in separate reports (M-H3.3.1 through M-H3.3.4) and serve as the starting point for more detailed planning over the following months. A post-hoc survey filled in by 75 attendees showed that the workshop had answered many organizational issues. But since the project has only started, many more issues must be discussed and clarified in the coming months, the survey showed. Overall, two thirds of the participants were satisfied with the organization oft he workshop.


BACKGROUND
Spontaneous pneumomediastinum is a rare entity that usually occurs in young males without any apparent precipitating factor. Several case series have been published focusing on clinical features, workup and prognosis. Due to the rarity of this entity, there is no consensus on the most appropriate treatment.

OBJECTIVES
To describe the clinical characteristics and course of patients with spontaneous pneumomediastinum in our institution.

METHODS
This retrospective descriptive study was based on a review of the charts of all patients discharged from our hospital with a diagnosis of SPM during the period 2000 to 2007. Thirteen patients were identified and information on their clinical presentation, course, hospital stay, investigations and outcome was gathered.

RESULTS
In 70% of patients the presenting complaint of SPM was pleuritic chest pain, while 30% of patients developed SPM in the course of another respiratory illness. Subcutaneous emphysema was the most common clinical finding (46%). Chest X-ray was diagnostic in 12 of 13 patients, and additional tests such as esophagogram and echocardiogram were unrevealing. Leukocytosis and electrocardiographic changes in inferior leads were seen in 30% of patients. Mean hospital stay was 48 hours, treatment was supportive, and symptomatic improvement was usually noted within 24 hours. No recurrences occurred.

CONCLUSIONS
SPM is a rare entity that should be considered in patients with pleuritic chest pain. Treatment is supportive, and if no clues for esophageal rupture are present, investigations other than chest X-ray are probably not warranted. It is safe to discharge the patient within 24 hours provided that symptomatic improvement is achieved.


Introduction Hydroxypyrones are highly versatile molecules and several members of this family, both alone and in combination with metals, were found to exert anti-proliferative activities against a wide range of tumor cells. In this study, we show the anti-tumor potential of the prototype of new molecules belonging to the family of hydroxypyrones, named maltonis [4(N),10(N)-bis[(3- hydroxy-4-pyron-2-yl)methyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane], in different tumor cell lines (derived from both hematopoietic and solid human tumors). Methods and Results We examined the potential of maltonis to induce, in cell-free assays, covalent modifications of DNA structure, together with anticancer activities (cell growth inhibition, cell cycle perturbations, effects on programmed cell death). The cellular response to maltonis treatment was assessed also at the molecular level by evaluation of the transcript level of genes involved in cell cycle and programmed cell death regulation. The possible induction of a maltonis-mediated DNA damage response was investigated monitoring the histone H2AX phosphorylation (γH2AX). Sarcoma cell lines appeared to be particularly sensitive to maltonis in in vitro assays. Consistently, preliminary in vivo experiments reported a cytostatic effect of maltonis, monitoring a consistent reduction of the neoplastic lesions, when intra-tumor injected at doses of 20/40 mg/kg (for two weeks) in a xenograft model of Ewing Sarcoma. However, a range of different levels of sensitivity was observed in the different histotypes (osteosarcoma, Ewing sarcoma and rhabdomyosarcoma) and among cell lines, indicating the need of further studies to identify markers of efficacy. Conclusions Taken together, these results show that maltonis appears to be a good candidate for sarcoma treatment. It induces complex DNA structural modifications, which need to be further analysed in order to clarify mechanisms of action and efficacy of this new drug. Grants from: AIRC 10452 and Ministry of Health_RF2008 to KS; A.S.S.O., PRIN 2008 and PRIN 2009 to MF and VF. Citation Format: Maria Cristina Manara, Mirco Fanelli, Stefano Amatori, Clara Guerzoni, Lorena Landuzzi, Pier-Luigi Lollini, Luca Giorgi, Vieri Fusi, Katia Scotlandi. Molecular properties and antiproliferative activity against tumor cells of a new poly-alkylamino-bis-maltolic synthetic molecule (maltonis). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2768. doi:10.1158/1538-7445.AM2013-2768


The influence of dominant electron heating on internal transport barriers (ITBs) was investigated in JT-60U. The electron cyclotron waves were mainly utilized in order to extend the experimental space into a dominant electron heating regime. The experiments were carried out on both reversed magnetic shear (RS) and positive magnetic shear (PS) plasmas. It was found that in RS plasmas clear ITBs in Te, Ti and ne profiles remained even under dominant electron heating. Energy confinement in excess of twice the H-mode scaling has been obtained in the regime. On the other hand, it was found that in PS plasmas the Ti ITB was degraded by dominant electron heating.


Background Lintuzumab, a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest activity against AML. To increase the antibody's potency yet avoid nonspecific cytotoxicity seen with β-emitting isotopes, the isotope generator 225Ac (t½=10 days), which yields 4 α-particles, was conjugated to lintuzumab. A phase I trial demonstrated that 225Ac-lintuzumab is safe at doses ≤ 3 μCi/kg and has anti-leukemic activity across all dose levels studied (Jurcic et al. ASH, 2011). We are conducting a multicenter, phase I dose escalation trial to determine the maximum tolerated dose (MTD), toxicity, and biological activity of fractionated-dose 225Ac-lintuzumab in combination with LDAC.

Patients and Methods Patients ≥ 60 yrs who had untreated AML with poor-prognostic factors, such as an antecedent hematologic disorder (AHD), unfavorable cytogenetic or molecular abnormalities, and significant comorbidities, were eligible. Patients received LDAC 20 mg bid for 10 days every 4-6 weeks. During cycle 1, beginning 4-7 days after LDAC, two doses of 225Ac-lintuzumab were given approximately one week apart.

Results Seven patients (median age, 76 yrs; range, 72-80 yrs) were treated, all of whom had AHDs. Five (71%) had intermediate-risk cytogenetics, and two (29%) had unfavorable cytogenetics. The median CD33 expression was 76% (range, 69-95%). Prior therapy for myelodysplastic syndrome included hypomethylating agents (n=4) and allogeneic hematopoietic cell transplantation (n=1). Patients received 225Ac-lintuzumab at doses of 0.5 (n=3) or 1 (n=4) μCi/kg/fraction, two fractions per patient (total administered activity, 68-199 μCi). Dose-limiting toxicity was seen in one patient receiving 1 μCi/kg/fraction who had grade 4 thrombocytopenia in the setting of an aplastic bone marrow that persisted > 6 wks after completing the second fraction of 225Ac-lintuzumab. Other toxicities included grade 3 febrile neutropenia (n=5), bacteremia (n=1), pneumonia (n=1), cellulitis (n=1), transient increase in creatinine (n=1), and generalized weakness (n=1). Bone marrow blast reductions were seen in 4 of 6 evaluable patients (67%) after cycle 1 (mean blast reduction, 58%; range, 34-100%). No CRs, however, were observed. The median number of cycles administered was 2 (range, 1-4), and the median time to progression was 2.5 months (range, 2-7+ months).

Conclusions Fractionated-dose 225Ac-linutuzmab in combination with LDAC is feasible, safe, and has anti-leukemic activity. Accrual continues to define the MTD, with planned dose levels up to 2 μCi/kg/fraction. Additional patients will be treated at the MTD in the phase II portion of this trial to determine response rate, progression-free survival, and overall survival.

Disclosures: Jurcic: Actinium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Ravandi: Actinium Pharmaceuticals, Inc.: Research Funding. Pagel: Actinium Pharmaceuticals, Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Park: Actinium Pharmaceuticals, Inc.: Research Funding. Douer: Actinium Pharmaceuticals, Inc.: Research Funding. Estey: Actinium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Cicic: Actinium Pharmaceuticals, Inc.: Employment, Equity Ownership. Scheinberg: Actinium Pharmaceuticals, Inc.: Ac-225-Lintuzumab, Ac-225-Lintuzumab Patents & Royalties, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.


A rotational scanning technique useful in microwave holography is developed. This technique has the special feature that the recording structure can be constructed on a smaller scale than a conventional scanning technique, and that a lensless Fourier transform hologram is obtainable. The theoretical aspect of this new holographic arrangement and experimental evidence in support of the theory are presented.


This is a brief review of alternative methods of problem-solving in geoscience with emphasis on the role of mathematical geology. It is desirable to maintain a clear-cut distinction between reliable facts which can be stored in data banks and concepts that can be incorporated in the specifications of statistical models designed for specific purposes. If possible, subjective probabilities should be incorporated in hypotheses that are to be tested by statistical inference.


The authors have discussed the numerical simulation method for transient electromagnetic fields using the boundary element method which is based on scalar and vector potentials. To use the BEM which is based on potentials to transient electromagnetic fields, a special gauge transformation has been performed to get an appropriate boundary condition for potentials. This paper discusses a restriction on the topological configuration of the considered region, that is necessitated by the use of the gauge transformation. The discussion is done using the four-dimensional space-time formulation. It is shown that the BEM which is based on potentials is almost free from a topological restriction on the considered region.


Proc Amer Assoc Cancer Res, Volume 46, 2005

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CD44 is an adhesion molecule present on a wide variety of cells, including mammary epithelial tumor cells. However, the role of CD44 in tumor progression is a controversial one. While many believe CD44 to promote tumor progression, others believe CD44 is not involved in tumor progression and may even be protective against invasion. To firmly establish the role of CD44 in breast cancer metastasis, MMTV-PyMT transgenic and MMTV-PyMT CD44-/- bitransgenic mouse tumor progression and metastatic lung tumor formation were evaluated. No difference was observed in the rate of primary tumor formation. However, MMTV-PyMT CD44-/- bitransgenic mice had a 67% incidence of metastasis compared to a 16% incidence on the MMTV-PyMT control mice. Additionally, the average number of metastatic tumors per mouse was also higher in the in the CD44 null mice. Together these findings suggests that CD44 does not play a role in tumor progression, but rather, plays a role in delaying metastatic tumor formation. To resolve the cause of the increased number of metastatic pulmonary tumors in the absence of CD44, we have looked at the expression patterns of the CD44 and its ligand Hyaluronan (HA). CD44 expression is found throughout the mammary tumor epithelium while HA expression is limited to the stromal area surrounding the tumor. This led us to investigate which cells may be responsible for HA production in mammary tumor tissue through the use of an MMTV-PyMT Has2-GFP bitransgenic mice. The Has2-GFP mouse expresses GFP under the control of the promoter for an HA producing enzyme, Has2. Anti-GFP staining shows tumor epithelial cells do not produce HA. Rather, cells within the stromal compartment surrounding the tumor are responsible for Has2 mediated HA production. Since HA production is mediated by stromal cells we designed an invasion assay that would mimic cellular invasion into a 3 dimensional matrix that contained immobilized HA similar to the stromal compartment surrounding tumors. We subjected 3 CD44 positive metastatic breast cancer cell lines to the assay. In each case invasion into gels cast with HA occurred at a rate significantly lower than invasion into gels that contained no HA. These result suggest that the presence of HA in a matrix may function to inhibit cellular invasion. To test whether HA mediated inhibition of invasion was a CD44 dependant event, we incubated the invasive breast cancer cell line MDA-MB-231 with a CD44 blocking antibody prior to the addition to the invasion assay. Invasion into gels containing no HA did not differ with or withoutwithout the blocking antibody. However, cellular invasion into gels containing HA was higher in the presence of the blocking antibody. In fact, invasion into HA containing gels with the blocking antibody was even higher than into gels that contained no HA. Therefore, while HA may inhibit cellular invasion in the presence of CD44, the absence of CD44 may promote HA mediated invasion.


The gut microbiome is considered an endocrine organ that can influence distant organs and associated biological pathways. Recent advances suggest that gut microbial homeostasis is essential for reproductive health and that perturbations in the gut microbiota can lead to reproductive pathologies. This review provides an updated overview of the relationship between the gut microbiome and female reproductive diseases. Specifically, we highlight the most recent findings on the gut microbiome in gynecological pathologies including polycystic ovarian syndrome (PCOS), endometriosis, and endometrial cancer. Most studies revealed associations between altered gut microbial compositions and these reproductive diseases, though few have suggested cause-effect relationships. Future studies should focus on determining the molecular mechanisms underlying associations between gut microbiota and reproductive diseases. Understanding this bidirectional relationship could lead to the development of novel and effective strategies to prevent, diagnose and treat female reproductive organ-related diseases.


This paper presents a system for automatically generating discourse structures from written text. The system is divided into two levels: sentence-level and text-level. The sentence-level discourse parser uses syntactic information and cue phrases to segment sentences into elementary discourse units and to generate discourse structures of sentences. At the text-level, constraints about textual adjacency and textual organization are integrated in a beam search in order to generate best discourse structures. The experiments were done with documents from the RST Discourse Treebank. It shows promising results in a reasonable search space compared to the discourse trees generated by human analysts.


ABSTRACT Opportunities to track environmental changes over more than a century are rare in tropical mountains. Edward Whymper's survey of flora and fauna on the summit of Mt. Corazón (Ecuador, 4788 m a.s.l.) in 1880 provides a unique opportunity to compare historical observations with the current composition of plant and insect communities on a tropical alpine mountain top. We studied Whymper's archives and historic specimens in London and Paris, and performed a resurvey of vascular plants and ground beetles (Coleoptera Carabidae) in January 2020. Currently, a large part of the summit area of Corazón is heavily damaged by trampling and stone removal due to mountain tourism, and no vascular plants are present in the deteriorated area on the top of the ridge. However, more species were collected in 2020 than in 1880: 22 of vascular plants vs. 7, and 4 of ground beetles vs. 1. Upslope shifts over 140 years may partly explain this increase in species richness, although the low numbers of Whymper's sampling may also be due to less skilled collectors and to the presence of permanent snow beds on the summit. The current faunistic and floristic data presented in this contribution can be used as a baseline for future resurveys of Corazón, in order to monitor changes in the species distribution and community composition of its summit area. Owing to the very small area of its superpáramo and to the soil deterioration by trampling along the summit ridge, Corazón is especially exposed to the effects of climate change and to the risk of extirpation of endemic cold-adapted specialists.


After the explosions of December 1977 intense scrutiny was given to the occurrence of fires and explosions in grain handling and processing facilities in the United States. The conditions leading to fires and explosions in these facilities-fuel, oxidizer, ignition, mixing, and confinement-had been identified immediately following World War I. At the beginning of this decade the National Academy of Sciences investigated 14 explosion incidents, reported on the findings, and made recommendations concerning accident prevention. As the decade has progressed, however, these fires and explosions have continued with reports of investigations being available for some major incidents. The continuing critical factor in these explosions is the massive uncontrolled accumulations of fuel. In the effort to eliminate this industrial hazard, the U.S. Department of Labor has issued Draft Final Standards pertaining to safety hazards in grain-handling facilities. It is clear that it is technically feasible to eliminate fire and explosion hazards from the grain and agricultural products industry because these events do not occur as a result of unknown, unpreventable causes.