Characterization and epitope mapping of two monoclonal antibodies against human CD99

CD99 plays a critical role in the diapedesis of monocytes, T cell differentiation, and the transport of MHC molecules. Engagement of CD99 by agonistic monoclonal antibodies has been reported to trigger multifactorial events including T cell activation as well as cell-cell adhesion during hematopoietic cell differentiation. In this study, to identify the functional domains participating in the cellular events, we mapped the epitopes of CD99, which are recognized by two agonistic CD99 monoclonal antibodies, DN16 and YG32. Using recombinant fusion proteins of GST with whole or parts of CD99, we found that both antibodies interact with CD99 molecules independently of sugar moieties. DN16 mAb detected a linear epitope located in the amino terminal region of CD99 while YG32 mAb bound another linear epitope in the center of the extracellular domain. To confirm that the identified epitopes of CD99 are actually recognized by the two mAbs, we showed the presence of physical interaction between the mAbs and the fusion proteins or synthetic peptides containing the corresponding epitopes using surface plasmon resonance analyses. The dissociation constants of DN16 and YG32 mAbs for the antigen were calculated as 1.27 x 10(-7) and 7.08 x 10(-9) M, respectively. These studies will help understand the functional domains and the subsequent signaling mechanism of CD99.     

Intermolecular and intramolecular Diels-Alder cycloadditions of 3-ylidenepiperazine-2,5-diones and 5-acyloxy-2(1h)-pyrazinones

The 3-ylidenepiperazine-2,5-diones 16 and 39 and 5-acyloxy-2(1H)-pyrazinones 17 can serve as starting materials for the Diels-Alder reactions of alkenes and alkynes to the piperazine ring, under acidic conditions or in the presence of acetyl chloride, to afford tricyclic piperazine-2,5-diones 19, 20, 23-25, 27, 44, and 45. Intramolecular cycloadditions occur if 3-ylidenepiperazine-2,5-diones 30 and 32 are used as the starting materials. This procedure is a convenient path to bridged bicyclo[2.2.2]diazaoctane ring systems such as 31 and 33, the former being found in biologically active secondary mold metabolites, such as VM55599 (1) or brevianamide A (5), which have been isolated from various fungi. The synthesis of the indole compound 31 provided evidence for the proposed biochemical pathway with a Diels-Alder reaction as key step. Quantum chemical calculations have revealed that piperazinones with a cationic azadiene moiety are the most reactive species in Diels-Alder cycloadditions.     

Solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides

A novel solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides has been developed using FDMP resin with a carboxamide as the anchor point. With this approach, three points of diversity were incorporated into a GPCR-directed scaffold. Final products were obtained in good purity and yield.     

A new synthesis of 1,2,3,5‐tetrahydroimidazo[2,3‐b]‐[1,3]benzodiazocines

A new synthesis of 6‐carbomethoxy‐1,2,3,5‐tetrahydroirnidazo[2,3‐b][1,3]benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2‐(1‐aziridinylmethyl)‐3‐(2‐ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. The latter were readily obtained from 2‐nitrobenzalde‐hyde with methyl acrylate through the Baylis‐Hillman reaction.     

高能闪光照相中影响光程确定的几个因素

 利用闪光照相基本原理和成像原理，在直接记录法和转换屏记录法的情况下，研究了闪光照相中影响X射线在材料中光程确定的主要因素。结果表明，影响光程确定的几个因素是：散射效应、光源角分布效应、立体角效应和能谱效应。对于高能闪光照相，散射效应是影响光程确定的最主要因素，散射的存在使光程的测量值比实际值降低20%～40%。因此必须在做CT之前，对散射的影响进行修正。     

Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (−637.5 kJ mol⁻¹) than for adenosine diphosphate (ADP) (−578.2 kJ mol⁻¹). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP–ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

Mitochondria-targeting nucleopeptide (MNP) can sequester ATP by self-assembling with ATP. A small nanosized MNP/ADP complex forms a large assembly with ATP. Thus, intramitochondrial co-assembly causes stress by large structures and apoptosis.     

An Upper Bound for the w-Weak Global Dimension of Pullbacks

Let R be a commutative ring with identity and I0 an ideal of R.We introduce and study the c-weak global dimension c-w.gl.dim(R/I0) of the factor ring R/I0.Let T be a w-linked extension of R,and we also introduce the wR-weak global dimension wR-w.gl.dim(T) of T.We show that the ring T with wR-w.gl.dim(T) =0 is exactly a field and the ring T with wR-w.gl.dim(T) ≤ 1 is exactly a PwRMD.As an application,we give an upper bound for the w-weak global dimension of a Cartesian square (RDTF,M).More precisely,if T is w-linked over R,then w-w.gl.dim(R) ≤ max{wR-w.gl.dim(T) + w-fdR T,c-w.gl.dim(D) + w-fdn D}.Furthermore,for a Milnor square (RDTF,M),we obtain w-w.gl.dim(R) ≤ max{wR-w.gl.dim(T) + w-fdR T,w-w.gl.dim(D) + w-fdR D}.