Multiple Keys for a Single Lock: The Unusual Structural Plasticity of the Nucleotidyltransferase (4′)/Kanamycin Complex

The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme‐catalysed chemical modification of the drug. Over the last two decades, significant efforts in medicinal chemistry have been focused on the design of non‐ inactivable antibiotics. Unfortunately, this strategy has met with limited success on account of the remarkably wide substrate specificity of aminoglycoside‐modifying enzymes. To understand the mechanisms behind substrate promiscuity, we have performed a comprehensive experimental and theoretical analysis of the molecular‐recognition processes that lead to antibiotic inactivation by Staphylococcus aureus nucleotidyltransferase 4′(ANT(4′)), a clinically relevant protein. According to our results, the ability of this enzyme to inactivate structurally diverse polycationic molecules relies on three specific features of the catalytic region. First, the dominant role of electrostatics in aminoglycoside recognition, in combination with the significant extension of the enzyme anionic regions, confers to the protein/antibiotic complex a highly dynamic character. The motion deduced for the bound antibiotic seem to be essential for the enzyme action and probably provide a mechanism to explore alternative drug inactivation modes. Second, the nucleotide recognition is exclusively mediated by the inorganic fragment. In fact, even inorganic triphosphate can be employed as a substrate. Third, ANT(4′) seems to be equipped with a duplicated basic catalyst that is able to promote drug inactivation through different reactive geometries. This particular combination of features explains the enzyme versatility and renders the design of non‐inactivable derivatives a challenging task.     

相干振动动力学和高分辨非线性光谱学：空气/二甲亚砜液体界面的比较

研究了空气/二甲亚砜界面C?H伸缩振动的自由诱导衰减的相干振动动力学和亚波数高分辨宽带和频振动光谱．对于特定分子体系,频率域光谱测量和时间域动力学测量原则上应获得相同的信息．但对具有耦合或者重叠在一起的若干振动模式的分子体系,通过时域或者频域测量以获取光谱和动力学信息细节均非易事．对于振动光谱并非过于复杂的空气/二甲亚砜界面,基于亚波数高分辨宽带和频振动光谱的频域测量较超快时域测量更有益于获取界面结构和相干动力学定量信     

The maximum number of columns in supersaturated designs with

Cheng and Tang [Biometrika, 88 (2001), pp. 1169–1174] derived an upper bound on the maximum number of columns that can be accommodated in a two‐symbol supersaturated design (SSD) for a given number of rows () and a maximum in absolute value correlation between any two columns (). In particular, they proved that for (mod ) and . However, the only known SSD satisfying this upper bound is when . By utilizing a computer search, we prove that for , and . These results are obtained by proving the nonexistence of certain resolvable incomplete blocks designs. The combinatorial properties of the RIBDs are used to reduce the search space. Our results improve the lower bound for SSDs with rows and columns, for , and . Finally, we show that a skew‐type Hadamard matrix of order can be used to construct an SSD with rows and columns that proves . Hence, we establish for and for all (mod ) such that . Our result also implies that when is a prime power and (mod ). We conjecture that for all and (mod ), where is the maximum number of equiangular lines in with pairwise angle .     

Isomorphisms of spaces with large distortion

Let K and S be locally compact Hausdorff spaces and let X be a strictly convex Banach space of finite dimension at least 2. In this paper, we prove that if there exists an isomorphism T from onto satisfying then K and S are homeomorphic. Here denotes the Schäffer constant of X. Even for the classical cases , and , this result is the X‐valued Banach–Stone theorem via isomorphism with the largest distortion that is known so far, namely . On the other hand, it is well known that this result is not true for , even though K and S are compact Hausdorff spaces.     

On Landis’ Conjecture in the Plane

In this paper we prove a quantitative form of Landis’ conjecture in the plane. Precisely, let W(z) be a measurable real vector-valued function and V(z) ≥0 be a real measurable scalar function, satisfying ‖W‖ _{L ^∞(R ²)} ≤ 1 and ‖V‖ _{L ^∞(R ²)} ≤ 1. Let u be a real solution of Δu ? ?(Wu) ? Vu = 0 in R ². Assume that u(0) = 1 and |u(z)| ≤exp (C ₀|z|). Then u satisfies inf _{|z 0| =R}  sup _{|z?z 0| <1}|u(z)| ≥exp (?CRlog R), where C depends on C ₀. In addition to the case of the whole plane, we also establish a quantitative form of Landis’ conjecture defined in an exterior domain.     

Synthesis of Some C‐3,4,5‐Substituted 2,6‐Dimethyl‐1,4‐dihydropyridines (4‐DHPs)

A series of C‐3,4,5‐substituted 2,6‐dimethyl‐1,4‐dihydropyridines (1,4‐DHPs) with pharmacological properties were prepared by a variation from the classical Hantzsch synthesis. The procedure involves treatment of the respective aldehyde with either ethyl‐3‐aminocrotonate or 3‐aminocrotonitrile in anhydrous acetic acid at temperatures not exceeding 60°C, thus minimizing by‐product formation. The structures of title compounds were elucidated by ¹H NMR, ¹³C NMR, FTIR, and elemental analysis.     

Achiral diacrylate with an anticlinic smectic phase

We present an achiral diacrylate that shows a phase transition from the synclinic smectic C phase (SmC) to the anticlinic smectic C (SmCalt). This last phase has been previously reported only for swallow-tailed or dimeric compounds. Our studies using differential scanning calorimetry, X-ray diffraction, polarizing optical microscopy and broad band dielectric spectroscopy suggest the existence of this mesophase in this bifunctional smectogen.     

Ideological Complex Systems: Mathematical Theory

The goal of this article is to build an abstract mathematical theory rather than a computational one of the process of transmission of ideology. The basis of much of the argument is Patten's Environment Theory that characterizes a system with its double environment (input or stimulus and output or response) and the existing interactions among them. Ideological processes are semiotic processes, and if in Patten's theory, the two environments are physical, in this theory ideological processes are physical and semiotic, as are stimulus and response. © 2014 Wiley Periodicals, Inc. Complexity 21: 47–65, 2015     

Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α₁-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α₁-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α₁-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α₁-adrenoceptor density in whole hypothalamus and the expression levels of α_1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α₁-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α_1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.