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남북 및 북미정상회담을 통해 북한의 비핵화 협상이 본격적으로 시작했다. 이번의 비핵화 협상은 과거 협상들과 달리 성공적인 결과를 도출할 가능성이 높을 것으로 판단된다. 그 이유는 첫째로 북한이 핵탄두의 경량화와 대륙간탄도탄 발사에 성공했기 때문에 미국의 대북정책 변화가 불가피 하다. 둘째, 김정은 정권은 국내적 정통성 확보를 위해 경제발전이 절대적으로 필요하며, 이를 위해 대북제재 해소는 물론이고 서방의 경제협력이 절실하다. 셋째, 김정은의 권력승계이후 교체된 남한과 미국의 리더십은 변화된 한반도 현실에 적극적으로 대응하고 있다. 물론 비핵화 문제는 북미협상에서 결정될 것이며, 남북관계 개선은 그 결과에 커다란 영향을 받을 것이다. 문제는 북미사이의 신뢰부재로 인해 비핵화협상이 결코 순조롭게 진행될 것으로 기대하기 어렵다는 점이다. 사실 비핵화 문제는 한반도 평화정착의 필요조건일 뿐이다. 한반도 평화정착을 위해서는 여러 차원의 충분조건들이 존재한다. 따라서 비핵화 협상은 한반도 평화정착을 위해 필요한 다양한 분야의 협력과 유관국들 사이의 상호이해가 연계적으로 추진되어야 하며, 여기에 한국정부가 감당해야 하는 여러 과제와 역할이 있다.

Binding affinity maturation without structure determination remains a difficult challenge in the computer-aided protein engineering. Precise binding mode identification is a vital prerequisite for the affinity maturation. However, pure computational methods have been unreliable in practice so far and experimental structural biology techniques are generally too costly. Herein, we show that computational epitope localization followed by the full-atom energy minimization with intermediate experimental validation can yield precisely bound complex model structure, which ultimately enables effective affinity maturation and redesign of binding specificity. As a proof-of-concept, we targeted a leucine-rich repeat (LRR) protein binder which specifically binds to the human IgG1 (hIgG1). Based on the computationally predicted binding mode of the LRR protein binder to hIgG1, the binding affinity of the protein binder was significantly increased and its specificity was redesigned toward multiple IgGs from other species. Experimental determination of the complex structure showed that the predicted model closely matched the X-ray crystal structure. Through the benchmark of therapeutically relevant existing LRR protein complexes, we demonstrate that the present approach can be broadly applicable to other proteins which undergo small conformational changes upon binding.Significance StatementComputer-aided design of binding affinity and specificity of two interacting proteins without structural determination is a challenging problem in protein engineering. Despite recent advances in the computational biology techniques, however, in silico evaluation of binding energies has proven to be extremely difficult. We show that, in the cases of protein-protein interactions where only small structural changes upon binding occur, partial experimental validation of binding can greatly complement the computational energy. Using an LRR (leucine-rich repeat) protein binder as a model system, the binding orientation of two binding partners was precisely dentified by the hybrid approach. Based on the predicted model, we could successfully redesign the binding affinity and specificity of the protein binder by the full-atom energy calculation.

A joint monitoring of dust-storms that occurred in East Asia from March until May 2003 has been carried. Our discussions include dust-storm observations in the source areas of China and Mongolia, and measurements with satellites and ground monitors in central Korea. Differences were found in the definition and measurement of dust-storms. Over the source area of Mongolia there were 6 dusty days in March, 18 days in April, and 10 dusty days in May. In Inner Mongolia of northern China there were 4 dust-storms with 14 dusty days observed over the three months. In central Korea, a sink area, there were 4 cases of weak dust-storm and 17 dusty days in the spring of 2003. The highest PM10 value was 607 μgm−3 and PM 2.3 was 149 μgm−3, respectively. These observations identify the growing need for further universal observation practices and dust-storm reporting in future.

탈냉전시기 북한사회에서 발생하는 다양한 모순과 갈등을 비롯하여 사회구조의 변화에 관한 연구결과들이 많이 있다. 그렇지만 이에 관한 연구는 크게 두 측면에서 어려움을 겪고 있다. 한편으로는 북한의 폐쇄성 탓에 그러한 사실을 입증할 수 있는 양적·질적 자료들이 절대적으로 부족한 현실과 다른 한편으로는 연구자의 북한에 대한 인식과 이에 따르는 방법론적 문제가 바로 그것이다. 이러한 두 문제를 당장 해결할 수 있는 적절한 대안이 없는 현실에서 독일사례는 우리에게 여러 가지 생각할 거리를 제공한다. 1970년대 사회주의체제 발전의 시기에 동독정권이 사회구조 변화와 내적 갈등에 대해 어떻게 인식하고 대응했는지, 또 서독학자들은 동독 사회변화를 설명하기 위해 어떻게 접근했고 그 연구결과가 어떠했는지를 정리해봄으로써 북한내부의 현실을 유추하고 우리의 북한사회연구를 위한 방법론적 과제와 전략을 모색하는데 도움을 얻을 가능성이 있기 때문이다. 이 맥락에서 본 논문은 독일과 한반도의 차이, 특히 동독과 북한의 상이성을 인정하되, 독일사례에서 우리가 창조적으로 활용할 수 있는 시사점을 마지막에 요약적으로 정리하고 있다.

The potency of nucleotide antagonists at P2Y1 receptors was enhanced by replacing the ribose moiety with a constrained carbocyclic ring (Nandanan, et al. J. Med. Chem. 2000, 43, 829—842). We have now synthesized ring-constrained methanocarba analogues (in which a fused cyclopropane moiety constrains the pseudosugar ring) of adenine and uracil nucleotides, the endogenous activators of P2Y receptors. Methanocarba-adenosine 5′-triphosphate (ATP) was fixed in either a Northern (N) or a Southern (S) conformation, as defined in the pseudorotational cycle. (N)-Methanocarba-uridine was prepared from the 1-amino-pseudosugar ring by treatment with β-ethoxyacryloyl cyanate and cyclization to form the uracil ring. Phosphorylation was carried out at the 5′-hydroxyl group through a multistep process: Reaction with phosphoramidite followed by oxidation provided the 5′-monophosphates, which then were treated with 1,1′-carbonyldiimidazole for condensation with additional phosphate groups. The ability of the analogues to stimulate phospholipase C through activation of turkey P2Y1 or human P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 receptors stably expressed in astrocytoma cells was measured. At recombinant human P2Y1 and P2Y2 receptors, (N)-methanocarba-ATP was 138- and 41-fold, respectively, more potent than racemic (S)-methanocarba-ATP as an agonist. (N)-methanocarba-ATP activated P2Y11 receptors with a potency similar to ATP. (N)-Methanocarba-uridine 5′-triphosphate (UTP) was equipotent to UTP as an agonist at human P2Y2 receptors and also activated P2Y4 receptors with an EC50 of 85 nM. (N)-Methanocarba-uridine 5′-diphosphate (UDP) was inactive at the hP2Y6 receptor. The vascular effects of (N)-methanocarba-UTP and (N)-methanocarba-UDP were studied in a model of the rat mesenteric artery. The triphosphate was more potent than UTP in inducing a dilatory P2Y4 response (pEC50 = 6.1 ± 0.2), while the diphosphate was inactive as either an agonist or antagonist in a P2Y6 receptor-mediated contractile response. Our results suggest that new nucleotide agonists may be designed on the basis of the (N) conformation that favors selectivity for P2Y1, P2Y2, P2Y4, and P2Y11 receptors.

Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y1 receptors.

As one of the main industrial pollutants, aromatic solvents such as benzene, toluene, and xylenes (collectively known as BTX) have been causing the detrimental effects on environment 1-5]. Much effort has been made on the elimination of these compounds from a waste stream, and various methods have been reported [3-5]. In biological treatment system, three types of processes have been developed: bioscrubber, trickling filter, and biofilter[3,5]. Because of low solubility in water and high volatility, BTX are usually fed into the degradation process in gas phase with air stream [3]. In conventional processes, however, volumetric degradation rate was relatively low, less than 0.04 g/L/h, and efficient control of operational conditions such as moisture content in the bed and transfer rate of compounds to be treated was reported to be difficult to realize [3].