Zeng state cemetery at Zaoshulin during the Spring and Autumn period, Suizhou, Hubei

The Zaoshulin cemetery includes five large tombs with an entry ramp leading to a central chamber on one side, 19 medium tombs, and 62 small tombs. According to the inscriptions on the bronze vessels, the layout of the tombs, and the grave assemblages, this cemetery was the burial place for the high-ranking noblemen of the Zeng state. Three hierarchies of tombs from large to small in size correspond to the social ranks of marquises, high-ranking noblemen, and low-ranking noblemen. Amongst these tombs, the occupants of five large burials in three groups are identified as Lord Qiu of Zeng and his wife Yu, Marquis Bao of Zeng and his wife Mi Jia, and Marquis De of Zeng. The Zaoshulin cemetery, along with the sites and cemeteries at Yejiashan, Wenfengta, Guojiamiao, Sujialong, presents a clear and complete archaeological sequence of the culture of Zeng. It also establishes a reference point for Bronze Age archaeological culture in South China.

Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability

Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor populations present. In this work, we used a microfluidic device to study tumor metabolic vulnerability to several metabolic inhibitors. The microdevice included a central chamber to culture tumor cells in a three-dimensional (3D) matrix, and a lumen in one of the chamber flanks. This design created an asymmetric nutrient distribution across the central chamber, generating gradients of cell viability. The results revealed that tumor cells located in a nutrient-enriched environment showed low to no sensitivity to metabolic inhibitors targeting glycolysis, fatty acid oxidation, or oxidative phosphorylation. Conversely, when cell density inside of the model was increased, compromising nutrient supply, the addition of these metabolic inhibitors disrupted cellular redox balance and led to tumor cell death.

A novel 3-dimensional (3D) microfluidics device to model the tumor microenvironment (TME).

704 Background: In vitro models of cancer have led to significant therapeutic advances. Despite the widespread use of in vitro tissue culture, the ability to directly evaluate human biology is limited by the inability to model the complex, 3D nature of the TME. We introduce a novel, microfluidic-based system of 3D human micro-tumors perfused with a network of human micro-vessels which could overcome the shortcomings of current in vitro systems. Methods: The micro-device was created by casting polydimethylsiloxane (PDMS) onto master molds, which are then bonded to a flat PDMS sheet using air plasma. Normal human lung fibroblasts (NHLF) and GFP labelled endothelial colony forming cell derived endothelial cells (EC-FCECs) were loaded in a fibrin gel at a 1:2 ratio into the central tissue chamber. Media was introduced through the microfluidic lines. The vascular network was developed with complete EGM2 media under nominal interstitial flow. Colorectal tumor cell lines labelled with mCherry were loaded to the side chambers on the seventh day after NHLF and EC loading. Bevacizumab or TGF- β were added on the second day after tumor cell loading. Results: Micro-vessels formed in the central chamber in 5-7 days after loading. The vessels were perfused with 70KDa fluorescent (red) dextran, and displayed intact vessel wall barrier. A suspension of a colorectal tumor cell line was loaded into the device side chambers, next to a fully developed vasculature. The tumor cells drove angiogenesis into the side chambers, and at the same time tumor began to migrate into the central chamber and within the vessel lumen. The angiogenesis induced by tumor cells can be pharmacologically inhibited, and the migration/ intravasation of tumor cells can be stimulated by TGF-β. Conclusions: Our novel micro-device system can be used as a functional in vitro system that can model the tumor micro-environment. This system has the advantage over current in vitro and in vivo systems in that it is high-throughput, rapid, cost-effective, and recreates many features of the 3D TME. We are currently expanding the platform to incorporate immune cells and designing a completely autologous system to test cancer immunotherapeutics.

Synaptic transmission in simple motility reflex pathways excited by distension in guinea pig distal colon

We examined specific receptor/transmitter combinations used at functionally identified synapses in ascending and descending reflex pathways of guinea pig distal colon. Excitatory (EJPs) or inhibitory junction potentials (IJPs) were recorded intracellularly from nicardipine-paralyzed circular smooth muscle in either the oral or anal recording chamber of a three-chambered organ bath, respectively. Blockade of synaptic transmission in the central chamber with a 0.25 mM Ca2+/12 mM Mg2+ solution abolished EJPs evoked by distension applied either in the central or the far (anal) chamber. IJPs evoked by distension in the central or the far (oral) chamber were depressed to ∼50% of control. Hexamethonium (nicotinic receptor antagonist, 200 μM) in the central chamber reduced IJPs evoked by far or central distension to 50%, whereas EJPs evoked by far distension were abolished and EJPs evoked by central distension were reduced to 70% of control. Hexamethonium in the recording chambers reduced both IJPs and EJPs evoked by central distension to ∼50%. EJPs in the ascending pathway were unaffected by blockade of muscarinic receptors in the central chamber or blockade of neurokinin 3 tachykinin receptors in this or the recording chamber. In the descending pathway, blockade of P2 receptors in the same chambers had only a minor effect on distension-evoked IJPs. Thus some intrinsic sensory neurons of guinea pig colon have long descending projections (>30 mm), but ascending projections of <15 mm. In contrast to the ileum, transmission between ascending or descending interneurons and from sensory neurons to descending interneurons is predominantly via nicotinic receptors; but transmission to inhibitory or excitatory motoneurons and from sensory neurons to ascending interneurons involves nicotinic and other unidentified receptors.

Evaluation of Several Dosing Regimens of Cefepime, with Various Simulations of Renal Function, against Clinical Isolates ofPseudomonas aeruginosa in a Pharmacodynamic Infection Model

ABSTRACT The objectives of this study were as follows: (i) to examine the killing activity of 2-g doses of cefepime against two clinical isolates (mucoid and nonmucoid) of Pseudomonas aeruginosa in a pharmacodynamic in vitro infection model, (ii) to compare the percentage of time above the MIC (T > MIC) for each of the regimens against P. aeruginosa, and (iii) to evaluate the area under the bactericidal curve for each regimen. Cefepime was administered at intervals of 8, 12, and 24 h with and without tobramycin, and two different levels of renal function were simulated: normal (creatinine clearance [CLCR] = 90 ml/min) and decreased (CRCL = 60 ml/min). Also, the killing activity of cefepime with and without tobramycin was compared to the killing activity of ceftazidime (2 g every 8 h) with and without tobramycin. The T > MIC was 100% in the central chamber except for the regimen in which cefepime was administered every 12 h and the CLCR was 90 ml/min, which provided concentrations above the MIC for 92% of the dosing interval against the C31 (mucoid; MIC of cefepime, 4 μg/ml) isolate and for 75% of the interval against the C34 (nonmucoid; MIC of cefepime, 8 μg/ml) isolate. All cefepime and ceftazidime monotherapy simulations resulted in 99.9% killing of the nonmucoid isolate within 4 to 8 h and within 4 to 6 h, respectively. Against the mucoid isolate, 99.9% killing was achieved only with combination therapy. The results of this study indicate that cefepime dosed at 2 g every 12 h under conditions of normal renal function and every 24 h with decreased creatinine clearance (60 ml/min) is effective both as monotherapy and in combination therapy against a nonmucoid strain of P. aeruginosa. With cefepime MICs of 4 and 8 μg/ml, the single-agent regimens provided T > MIC values in the central chamber for 92 and ≥75% of the dosing interval against the mucoid and nonmucoid isolates, respectively. Cefepime dosed at 2 g every 12 h, with a creatinine clearance of 90 ml/min, and every 24 h, with a creatinine clearance of 60 ml/min, resulted in killing activity equivalent to that of ceftazidime dosed at 2 g every 8 h. None of the monotherapies provided adequate killing of the mucoid strain of P. aeruginosa despite drug concentrations being above the MIC for ≥92% of all dosing intervals. Finally, combination therapy with tobramycin and either cefepime or ceftazidime enhanced the killing of both the mucoid and nonmucoidP. aeruginosa isolates.

The Anatomy of Eubothrium crassum (Bloch) from the Pyloric Caeca and Small Intestine of Salmo trutta L.

1. Eubothrium crassum (Bloch) is re-described with additional information about the scolex and genitalia.2. Specific differences between E. crassum and E. salvelini are commented upon and figured.3. The second portion of the uterine duct lying between the central chamber of Mehlis's gland and the uterine sac is established as the “fertilization chamber”.4. Polar bodies and maturation divisions are described and figured in definite relationships with the ovum as evidence of normal maturation in a cestode.5. The position of the receptaculum seminis is determined and a new name, the “vagina sac”, is given to what was previously described as a receptaculum seminis. It is thought to serve for propulsion of male and female cells into the uterine duct.

The Mull Hill Circle, Isle of Man, and its Pottery

On Mull or Meayll Hill, a mile north-east of the Calf Sound, Isle of Man, is the remarkable megalithic monument known as the Mull Hill Circle. It is not a stone circle of normal type but consists of six T-shaped structures, each comprising two rectangular cists averaging 5 ft. 9 in. by 2 ft. 8 in., placed end to end with the inner end of each open and forming the head of the T, and approached by a short passage about 7 ft. long at right angles (the upright of the T). These pairs of cists are arranged in a circle some 50 ft. in diameter; each group distinct, with the cists placed tangentially and the passages leading radially outwards. They are so spaced as to leave a larger interval between the groups on the north and south to form two opposite ‘entrances ’. Apparently the entire circle of cists had originally been covered by a ring of stones and earth, the whole forming a ‘disc-barrow’, the bank of which contained chambers. There are vague indications of a central chamber or cist. The stone used in the construction of the monument was a local slate. No capstones remain to any cists or passages, but all appear to have been paved with flat slabs.