Schmaier Eva Schmelzer Marcus Schwaiger Frank Sciurba James A. Shayman Donna Shewach Rebecca Shilling Vijay Shivaswamy Imad Shureiqi Stephen Skaper Melissa Snyder Osama Soliman Peter Sporn Jack Stapleton Sokrates Stein Arthur Strauch Bodo Eckehard Strauer Ku0059436 Jakob Strom Hong-shuo Sun Mark Sussman Kathy Svoboda Andrew Talal Sakae Tanaka Jose Tanus-Santos Milton Taylor Beverly Teicher Patricia Teixeira Daniela Tirziu Jorn Tongers Jordi Torrelles Niels Tørring Cory Toth George C. Tsokos Antonino Tuttolomondo

Dimitrios Tziafas Mark Udden Mohammad Uddin Terry G. Unterman Celalettin Ustun Nosratola Vaziri Jelena Vekic Hector Ventura Gregory M. Vercellotti Vassilis Voudris Jil Waalen Hiroo Wada Richard L. Wahl Qin Wang Chunyu Wang Lorraine Ware Saman Warnakulasuriya Donald Wesson Christof Westenfelder “
“The Editors of Translational Research have retracted the article titled “Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus” by Harada et al. After an Investigation Committee on Scientific Misconduct was formed at Nagoya City University to investigate 19 articles written by Drs. Naoaki

Harada and Kenji Okajima, the committee brought one article, published in Translational Research, to our attention. The committee concluded that Figures 4D, 4E, 4G and 4H in Translational Research (Harada et al., 2011) were derived from the same photograph as Figures 8D, 8E, 8G PtdIns(3,4)P2 and 8H in the Journal http://www.selleckchem.com/JNK.html of Pharmacology and Experimental Therapeutics (Narimatsu et al., 2009). While Figures D and G represent control data in both articles, Figures 4E and 4H and Figures 8E and 8H represent data from two different sets of animals treated with either desalted deep sea water or donepezil, respectively. The Nagoya City University

Committee concluded that Figure 4 in Translational Research (Harada et al., 2011) contains fabricated data. After the Committee pointed out these fabrications to the authors, they replaced Figures 4A-4I and an Erratum was published in Translational Research (Transl Res. 2011 Dec;158(6):387). However, the Committee has informed us that they have been unsuccessful in confirming that the new figures are the appropriate ones. Attempts to contact Drs. Harada and Okajima were made through the Nagoya Committee, and the authors declined to respond. The Editors “
“We wish to acknowledge the outstanding contribution of our reviewers and Editorial Advisory Board. The quality and breadth of the Journal is only made possible by the dedicated efforts of our reviewers. Joseph Ahearn S. Ansar Ahmed Ziyad Al-Aly Mary Alpaugh Ajjai Alva Elias Anaissie David Archer Lois Arend Robert F. Ashman Muhammad Ashraf Ravi Ashwath Pal Aukrust Edwin Avery Abul Azad Rathindranath Baral Robert P.

Two specimens of Atlantic horse mackerel were collected in 2007–2008 during the annual monitoring of fish, carried out by the research vessel SNB-AR-1 (University of Agriculture, Szczecin) in a network of areas along the western Polish coasts of the Baltic Sea with the aim of following the development of coastal fish stocks. All monitoring areas were located close to the coast. The other fish species were caught by accident by local fishermen with flounder gillnets or fyke nets (Figure 1). In 2007–2008 representatives of the following species were captured and examined: 1. two juveniles [(1) and (2)] of Atlantic horse mackerel

Tacrolimus nmr Trachurus trachurus L., 1758; Fam. Carangidae, Order: Perciformes; location: Pomeranian Bay, depth: 12 m; bottom trawl; date of capture: 30 September 2007; both individuals immature; All the specimens were INNO-406 in vitro examined morphologically following Krzykawski et al., 2001, Turan, 2006 and Uiblein and Heemstra, 2010. Species were identified with the aid of available keys (Whitehead et al. 1986). Table 2 lists detailed taxonomic data of the striped red mullet in

order to rule out any doubts about the species’ taxonomic status. In addition, the stomach contents of the fish were analysed. Parasitological examination focused on the skin, vitreous humour, eye lens, mouth and nasal cavities, gills, gonads, spleen, gastrointestinal tract, kidneys, swim bladder, peritoneum and muscles. The parasites found in the fish were prepared for species determination by viewing the specimens in transient light, immersed in glycerine GNAT2 or preserved in 70% ethanol so that the procedure could be continued the next day. Table 1 presents biological descriptions (total length, weight and stomach contents) of the fish examined. The stomachs of all the fish were empty, except that of the thicklip grey mullet from

the first location – (1), in which two specimens of Gammarus pulex (L., 1758) (Gammaridae) were found. Morphological examination of the specimens showed that they fit within the ranges given in Whitehead et al., 1986 and Krzykawski et al., 2001, with the exception of the striped red mullet (Figure 2), which also exhibited some features characteristic of Mullus barbatus L. (shape and length of head, barbel length, gill raker count). Table 2 lists the detailed morphological characteristics of the specimen of M. surmuletus examined, including the metric characters expressed as a proportion of total length (TL), standard length (SL) and head length (HL), and meristic features. The ‘visiting’ fishes hosted eight pathogens from four taxonomic groups: Protozoa (two species), Nematoda (three species), Acanthocephala (two species) and Mollusca (one species) (Table 3). The most numerous were nematodes (Secernentea: Anisakidae), recorded in fishes of three species.

BMPs have been frequently used in clinical trials with significant heterogeneity. A systematic review and metaanalysis on 11 trials observed comparable times to fracture healing between ABT 199 BMP and controls and confirmed some evidence of increased healing rates with BMP without a secondary procedure compared with usual care control in acute tibial fractures [47], but observed that achieving union for nonunited fractures was similar to bone graft substitutes. Other strategies such as local application of FGF2 were found to accelerate tibial shaft fractures [48], although no data are available in nonunions. Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal

tissue. In Europe, about one million patients encounter surgical bone reconstruction annually and the numbers are increasing due to our aging population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, I-BET-762 molecular weight but this is only attained when augmentation includes cells capable of forming bone. Other options to augment this bone repair include osteoinductive (i.e. bone inducers) and osteoconductive (i.e. bone guides) capabilities of the supplied coadjuvants to the surgical treatment. Bone autograft is the safest and most effective grafting procedure, since it contains a patient’s

own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), while providing a framework for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cm3) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequences of pain and complications [49]. The next solution is allograft bone directly coming from tissue banks (fresh-frozen) or prepared to be conserved (dried or lyophilized). This solution does not contain

living cells and some matrix proteins are destroyed by virus-inactivation treatments and the freezing Glutathione peroxidase process, thus it only guarantees osteoconductive properties. Moreover, allograft bone may transfer disease or lead to immunological rejections [50]. An interesting alternative is to combine allograft with MSCs from concentrated bone marrow, as has been proposed in bone defects after revision hip surgery [51] but also preliminarily explored in long bone pseudarthrosis [52]. Yet the number of cells may be an issue, as the available evidence in preclinical models recommends a high number of cells [53] and many ongoing clinical trials are thus based on high number of MSCs that require cell expansion, as will be discussed later. Since both autograft and allograft have drawbacks, scientists have long searched for biocompatible materials that could be used in place of the transplanted bone [50] and [54].

In an effort to increase the genomic resources and underpin future molecular investigations into this species, we have generated a transcriptome drawing on RNA from the head, skin and gastrointestinal (GI-) tract using 454 pyrosequencing. Atlantic halibut larvae were obtained from the aquaculture company Fiskeldi Eyjafjarðar Ltd. (Iceland) in December 2009. Larvae were reared in full-sea water using standard commercial procedures and normal metamorphosis was observed (Einarsdottir et al., 2006).

In brief, fertilised eggs from several spawning batches were hatched in an open system of egg incubators. Yolk sack larvae were transferred to silo-shaped (10 m3) through-flow systems in complete darkness at 5 °C until absorption of the yolk sack when they were moved to 100 l, round polyethylene start-feeding tanks containing sea-water at 10–11 °C under constant light conditions. The larvae were fed live Artemia ( Olsen Palbociclib et al., 1999) twice daily. Dead larvae were siphoned from the tanks each day and the mortality in each tank was registered. The larvae were euthanized with a lethal dose of MS-222 (50 mg·l− 1, ethyl 3-aminobenzoate methanesulfonate salt, Sigma-Aldrich, St. Louis, Akt inhibitor in vivo USA). Photographs were taken of each larvae and developmental staging was performed using myotome height and standard length (defined in Sæle et al., 2004) and then stored individually in RNAlater (Life Technologies, Carlsbad, USA) at − 20 °C. All handling

procedures followed the European guidelines (86/609/EU). Larvae were dissected into head, GI-tract and skin at standard development stages before, during and after

metamorphic climax (n = 6 per stage). Total RNA was extracted from all tissue/stages using a Maxwell®16 ADP ribosylation factor System (Promega, Madison, USA) and following the manufacturer’s instructions. Total RNA integrity was verified with an Agilent 2100 Bioanalyser (Agilent Technologies, Santa Clara, USA) and only the samples with RIN values equal to, or above 8 were used. cDNA libraries were prepared and sequenced at the Max Planck Genome Centre (Cologne, Germany), using 5 μg of total RNA obtained from a pool of 6 samples for each tissue/stage. First, the whole transcriptome was enriched by depletion of the ribosomal RNA (rRNA, 28S, 18S, 5.8S and 5S) using a RiboMinus™ Eukaryote Kit (Life Technologies, Carlsbad, USA) following the manufacturer’s instructions. Total RNA (after rRNA depletion) was used to construct sixteen cDNA libraries (head from stage 5; head, skin and GI-tract from stages 7, 8, and 9, Sæle et al., 2004; stage 9 samples were split into 3 groups, 9A, 9B and 9C to differentiate by eye position) using a cDNA Rapid Library Preparation Kit (Roche 454 Life Sciences, Branford, USA) following the manufacturer’s instructions. Each library had a unique barcode and was amplified by emulsion PCR and sequenced on the GS-FLX platform (Roche 454 Life Sciences, Branford, USA). 6,091,832 raw sequence reads (.

As a result, improvements in the accuracy of attenuation correction in the abdomen are considered a work in progress. Another challenge in attenuation correction in PET–MRI is to account

for attenuation due to the radiofrequency CHIR-99021 manufacturer (RF) coil (required for all MR acquisitions) which has been shown to adversely affect the quantitative accuracy of PET emission data by significant amounts [46]. As the coil does not appear in the MR image, its attenuation must be accounted for separately in an MR-based approach. One recent study provided evidence that a using a high-exposure CT to obtain a model of (in this particular case) a head coil could be used in a model-based correction that gave attenuation-corrected PET images that

were comparable to the reference PET–CT reconstruction [47]. The authors noted that if there were errors in the positioning of the coil (on the order of a few millimeters), then artifacts emerged in the reconstructed PET image. Tellman et al. found similar results on the importance of coil alignment [48]. Alectinib cost Though challenging, careful engineering should adequately address this problem, as the geometry and composition of MR RF coils can be fixed for most, though not all, coil designs. Integration of PET/MR systems with advanced flexible coil designs, or endoscopic coils such as endorectal coils for prostate imaging, may require additional materials engineering work in reducing BCKDHB net attenuation of such designs, or real-time feedback on their location. Besides the use of MR data to correct for the effect of attenuation on PET data, simultaneously acquired MR images also offer the potential to improve PET images by providing anatomical information that can be incorporated into the PET image reconstruction process. Statistical reconstruction

algorithms are replacing filtered backprojection as the method of choice for generating PET images from coincidence data, primarily because they provide a framework in which the physical properties of the data collection process can be modeled [49]. We expect different tissue types to exhibit different tracer uptake levels, so knowledge of tissue boundaries can be incorporated into the PET image reconstruction process to reduce blurring at those boundaries [50], [51] and [52]. While these methods have been applied to PET–CT as well as retrospectively co-registered PET–MRI data, simultaneously acquired MRI data offer superior soft-tissue contrast with the most accurate spatial registration. There are three major types of motion that must be considered during PET acquisition: gross motion (e.g., head movement or subtle patient repositioning due to discomfort), periodic movement (e.g., cardiac and respiratory motion), and internal shifting and distortion in the pelvic and abdominal regions (e.g., peristalsis).

As larger platelets are more reactive in response to stimuli, selective consumption of larger platelets might occur.

Consequently, the MPV of circulating platelets would be decreased. Micro- and macro-thromboembolic events are one of the major complications for patients with advanced NSCLC and can be fatal [27], [28] and [29]. Therefore, this may be a possible explanation for the poor prognosis of patients with a low MPV/PC ratio. The MPV and PC were also significant prognostic factors for OS in univariate analyses (P = −0.0270 and P = 0.0124, respectively). However, multivariate analysis did not indicate the superiority of them against the MPV/PC ratio when considered independently (HR of a low MPV/PC ratio: 1.668 [P = 0.0008], HR of a low MPV: 1.381 [P = 0.0121], and HR of a high PC: 1.380 [P = 0.0114]). Therefore, we concluded that the MPV/PC ratio was a more reliable and accurate selleck inhibitor biomarker than the MPV or PC alone. Despite the retrospective nature and small size of the present study, our results clearly demonstrated that a low MPV/PC ratio at initial diagnosis was an independent unfavorable prognostic factor

for patients with advanced NSCLC. Further investigation should clarify the etiology by which the amount and volume of circulating platelets modulate mortality in patients with NSCLC. The authors have declared no conflict of interest. “
“Over the past selleck kinase inhibitor Grape seed extract two decades, the

mortality attributed to lung cancer has increased and it is now the leading cause of cancer deaths [1]. Late diagnosis is a fundamental obstacle to improving the outcomes of lung cancer, with more than 70% of new cases presenting too late for curative treatment to be attempted [2]. Owing to the development of new chemotherapeutic agents, the costs of care for inoperable lung cancer are growing rapidly [3]. Therefore, it is worth examining the lifetime utility difference for patients with operable and inoperable lung cancer, which emphasizes the importance of early diagnosis of lung cancer. For the assessment of lifetime utility difference, both survival and quality-of-life (QoL) should be taken into consideration, and thus, the quality-adjusted life year (QALY) unit is more suitable than estimating survival alone for comparison of various types of healthcare services [4]. Quality-adjusted life expectancy (QALE) can be estimated via adjusting the survival function with the mean QoL at each time point, t, using the following equation [5], [6] and [7]: QALE=∫E[QoL(t/x)]S(t/x)dtQALE=∫EQoLt/xSt/xdtE[QoL(t/x)] denotes the expected value of health state (QoL) for patients with condition x at time t and S(t/x) denotes the survival function for condition x at time t. Previous studies discussing the benefits of surgery mostly focused on survival alone, and usually did not take lead-time bias into consideration [8].

Due to the dire consequences of early sexual activity[18], there have been efforts towards finding effective remedies to tame teenage sexual hyperactivity. In many Kenyan boarding schools, especially high schools, one such remedy that has

been used traditionally is crude kerosene. In a recent survey that we conducted using structured questionnaires at a Public University admitting students from all over the country, (data not shown) we found out that 68% female and 76% male first year, random respondents from 28 of 47 counties in Kenya, reported that at least one of their main meals (Lunch or Dinner) was supplemented with kerosene on daily basis during their high school years. Interestingly, over 60% of respondents in the above category gave why they thought kerosene was included in their diets as being to reduce their desire for sex. The remainder (40%) did not know Sirolimus why it was added. Kerosene is readily available and at fairly low costs throughout the country. The primary use is Selleck AG 14699 for lighting and in cooking stoves. Whether or not Kerosene supplementation is effective in reducing libido has not been scientifically tested. Further, the dietary use of kerosene in schools to tame sexual drive occurs with little or no care at all on its possible hazardous effects on the health status these students.

Although some information is currently available on the effect of dietary kerosene supplementation in animals and/or humans [12] and [19], such studies have failed to provide comprehensive information on effects on T levels, link to aggression and body tissue toxicity. The present

study was designed to monitor the effects on serum T levels, hematological, biochemical and histopathological changes in rats exposed to crude kerosene as a dietary supplement at doses that are comparable to those commonly used in Kenyan boarding schools. All the animal protocols Phosphoglycerate kinase and experiments were approved by the Institution animal care and use committee of the University of Eldoret (Protocol No.UOE/001/14). Male Wistar rats (rattus norvegicus) of approximately the same age (6 weeks old) corresponding to early adolescent boys [20] and similar body weights were obtained from the University of Eldoret animal facility. They were acclimatized and given free access to water and standard rodent chow diet (Unga Farmcare East Africa Limited, Nakuru, Kenya) for two weeks prior to initiation of the experimental diet. The rats were housed and maintained at ambient temperature of 250c under a photoperiod of 12 h of light and 12 h of darkness. The animals were assorted into three groups of five rats each with all groups having similar average serum testosterone levels. The sample size was determined according to the formula by Charan et.al.

Although we did not expose the pigs to OP in this preliminary study, we followed local clinical recommendations for the

treatment of OP casualties, which includes hyperventilation, to reduce OP-induced hypercapnia. In both cases respiratory rate was kept on 30 breaths per minute, and ventilation lasted for 25 minutes, with no oxygen supplementation. Both devices were effective in ventilating the animals. Physiological parameters were monitored continuously and no significant changes were observed. Vital signs included heart rate derived from ECG, O2 saturation by pulse-oximetry placed on the animals’ tails, non-invasive blood pressure and EtCO2. Ventilation was monitored by watching chest wall movement and blood saturation. Restrained pigs were fitted with an intravenous line Mitomycin C cost and anesthetized using Propofol (3.5 mg/kg, iv) to enable the insertion of an arterial cannula into the pigs’ ear. About 40 minutes later, when the pig regained full neck muscle tone,

exposure to paraoxon was performed. An intramuscular dose of 600 μg/kg paraoxon (the equivalent of 1.4LD50) was followed eight minutes later by a single administration of atropine (0.05 mg/kg, i.m.) alone, to simulate a realistic scenario, in which severe respiratory distress is likely to develop [21]. Following the paraoxon exposure three possible treatments were evaluated: Ventilation Belnacasan support using the biphasic cuirass device (Cuirass group, n = 7), ventilation support using a bag-valve mask (Mask group, n = 7) and a control

group that received no ventilation support (Control, n = 9). No oxygen enrichment was provided (FiO2 = 0.21). Ventilation was initiated 15 minutes following exposure and regardless of clinical manifestations was terminated 25 minutes later. Rate of ventilation was kept at 30 breaths per minute in Mirabegron both groups, with the same MRTX settings as in the preliminary study. Animals were closely observed for chest wall movement and post exposure signs. The following parameters were monitored continuously for one hour after paraoxon exposure: ECG, Heart rate (derived from ECG), O2 saturation by pulse-oximetry placed on the animals’ tails, and blood pressure by using an arterial line placed in the animals’ ear. Arterial blood gases (arterial pO2, arterial pCO2, arterial pH and BE) were collected from the arterial line before poisoning (0’) and 10, 20, 30, 40, and 50 minutes following exposure. The following clinical signs were recorded every 10 minutes during the first hour post exposure and 24 h later: fasciculation, salivation, teeth clenching, tremor, dermal patches, convulsion, and respiratory distress. The score ranged from 0 (no effect) to 3 (severe effect). Time of death within the 24 h was also recorded. All animals were allowed to recover with no further help, for a period of 24 hours. After 24 hours all animals were euthanized using i.v. overdose of sodium pentobarbital (200 mg/ml).

Since there are many possible PAHs precursors and the composition of coffee beans vary among species and cultivars, the formation and composition of these compounds might vary according to the coffee beans species (or cultivar) and the roasting conditions. Also, roasting process could be a concern, especially taking into account the Brazilian popular dark roasted coffee. Furthermore, the PAHs Pirfenidone transfer to the brew might be influenced

by the brewing procedure. Therefore, the objective of the present study was to evaluate the possible influence of coffee cultivar and roasting degree on the presence of four carcinogenic PAHs; the influence of brewing procedure on the PAHs transfer from ground roasted coffee to the brew; and verify if these factors would affect the intake of these compounds by the Brazilian population. Two coffee samples (C. arabica cv. Catuaí Amarelo IAC-62 and C. canephora cv. Apoatã IAC-2258) developed by the Agronomic Institute of Campinas (IAC) and cultivated in the region of Campinas-SP, Brazil, were collected in September 2009. Green coffee Enzalutamide datasheet beans were obtained by the dry method,

where coffee cherries were harvested, dried under the sun until achieving 12 g/100 g moisture content and then the dried outer parts were mechanically removed. Roasting process was performed in order to obtain samples with 3 roasting degrees: light, medium and dark. For this matter, batches of green coffee beans containing 1 kg each were roasted in a Probat roaster (Probatino model, Leogap, Curitiba, PR, Brazil) at 200 °C and roasting time of 7 min Cisplatin mw (for light roast), 10 min (medium roast) and 12 min (dark roast). The repeatability of the process was evaluated by performing the roasting process at least twice for each degree of roast. For C. arabica cv. Catuaí Amarelo the roasted samples obtained

were: two light, four medium and three dark; while for C. canephora cv. Apoatã resulting samples were: four light, two medium and three dark roasted coffees. Roasting degrees were determined, in three replicates, by the Agtron/SCAA Roast Color Classification System, using an E10-CP Agtron Coffee Roast Analyser (Agtron, Reno, NV, USA). Numeric results were correlated with the discs and the roasting degree as follows, no. 25–45: dark, no. 55–65: medium, no. 75–95: light. Roasted beans were stored in aluminized valve bags at −18 °C and ground immediately before the preparation of the beverages. For grinding, a La Cimbali Special grinder (Cimbali, Milano, Italy) with ring nut number 4 was used, providing an average particle size of 400 μm or less. All ground roasted coffee samples were then used to prepare coffee brews. Two brewing procedures were evaluated, using the same ground coffee/water ratio (50 g/500 mL): 1) Filtered coffee – water (92–96 °C) was left to drip onto ground coffee held in a paper filter; 2) Boiled coffee – water (25 °C) was added to the ground coffee, the mixture was boiled and then filtered in a paper filter.

For nearly two millennia, it was a symptom and symbol of China’s never-ending problems with “frontier barbarians” who worked continuously to harvest some of the nation’s wealth for themselves (Barfield, 1989). It survives very visibly to the present, albeit now in greatly dilapidated condition except for a few limited restorations. The new Qin emperor also created for his personal afterlife a huge mounded tomb almost half a square km in extent, still unexcavated but, according to recorded legend, containing

a detailed replica of the royal palace surrounded by rivers of mercury. Well-digging in 1974 led to the discovery, about two km away from this location, of a fully equipped “spirit army” buried in two large pits that FG-4592 in vitro included perhaps 3000 life-sized http://www.selleckchem.com/PD-1-PD-L1.html “terracotta warriors” and associated pottery models of horses, chariots, and weaponry. Excavations quickly captured world attention and the work continues, now sheltered and displayed beneath a vast metal hangar that could house a considerable fleet of the world’s largest jet airplanes (Fig. 2). The Zheng Guor Canal system, according to historical records created in 246 BC by the pre-imperial Qin State, was laid out over a course of some 200 km and linked two local rivers. It hugely expanded the agricultural output of the Qin region and helped afford its lord the economic wherewithal to gain

greater control tetracosactide over his rivals. Beyond the constructions subsequently ordered by Emperor Qin Shihuangdi there were also infrastructural projects sponsored by other wealthy “houses” of the region that we still see attested archeologically – dams, canals, vast irrigated agricultural fields, and roads – that are not as well preserved as the displays of royal wealth we see in the Qin emperor’s funereal Terracotta Army. Nevertheless,

these modifications are evident on the landscape and referred to in written records of the time. A third-century historical source quoted by Elvin (1993) vividly portrays the busy cultural landscape of the Qin and following Han periods: “The households of the powerful are [compounds] where one finds hundreds of ridge beams linked together. Their fertile fields fill the countryside. Their slaves throng in thousands, and their [military] retainers can be counted in tens of thousands. Their boats, carts, and their merchants spread out in every direction…. The valleys between the hills cannot contain their horses, cattle, sheep, and swine. The great array of huge mounded earth tombs inside the boundaries of modern Xi’an, created by the Han emperors who followed Qin Shihuangdi, further attests the Imperial capacity of the time for enormously labor-intensive construction projects that created large areas of anthropogenic landscape in the Wei River Valley. Each Han tomb was an artificial mountain that took armies of men and animals years to build.