(

3H

) Tobramycin was used as a probe to determine the relationship between the structure of aminoglycoside antibiotics and their ability to remove this drug from its higher affinity binding site on the ribosome. The dissacharide moieties (neamine, tobramine, gentamine) appeared to have a common binding site, whereas the kanosamine, garosamine and ribose moieties determined the specificity of this binding. Amikacin and butikacin behaved in an anomalous manner in spite of their close structural relationship to tobramycin.

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The activities of tobramycin derivatives acetylated and ethylated on the 6'-N, '-N and -N positions were examined. The MICs of these derivatives against tobramycin sensitive strains indicated that '-N-ethylated and 6'-N-ethylated derivatives have a fairly good activity, and confirmed that the -N position is the most important one for antibiotic activity since -N derivatives were less active. The MICs of these derivatives against tobramycin resistant strains, and their inactivation by tobramycin modifying enzymes were examined. These results showed that '-N or 6'-N ethylation protects the drug against inactivation by AAC(') or AAC(6'), respectively, and '-N-ethyltobramycin and 6'-N-ethyltobramycin were active against strains containing these modifying enzymes. On the other hand, -N ethylation protects the drug against inactivation by AAC() but -N-ethyl tobramycin does not inhibit strains containing this enzyme.

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A sample of [

3H

] tobrarnycin (5, 000 Ci/Mole) has been synthetized and incubated with
the bacterial ribosome and its subunits. The results obtained show that this antibiotic has
two types of binding sites. The primary one is probably responsible for the inhibition of
protein synthesis whereas the secondary one is probably related to the misreading and reading
tiirough of the messenger RNA.

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This paper is concerned with dynamics of the standard penetration test (SPT). The usefulness of mounting strain gages at two different stations along a driven rod is described, together with a workable procedure of analysis. The analysis procedure makes use of the traveling time between the two gage points and enables one to identify the particle velocity, the displacement and the stress at any station of the rod, as well as the energy actually transmitted from a hammer to the rod. Particular attention is called for the consequence of inevitable, small errors in strain data upon such identifications. A pertinent procedure of error-correction is proposed and its validity is substantiated against the performance of well instrumented SPTs performed by the authors.

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. The chromosome numbers of 64 species have been studied on which 56 are investigated for the first time.
. Morphological, anatomical and cytological findings on the Musaceae in the broad sense are considered from a phylogenetical standpoint and three distinct groups:
a) Musa-Ensete, ) Ravenala-Strelitzia-Phenakospermum and ) Holiconia are recognised as suggested by some authors. For these groups sub-familial status is proposed.
. Lowiaceae have been studied for the first time cytologically and their chromosome morphology, distinct from that of any other group of Zingiberales, confirms their claim to familial status.
4. Consideration of the conflicting theories proposed to account for the higher chromosome number in genera like Globba, Alpinia, and Phaemeria, etc. leads to rejection of Chakravorti's hypothesis of wholesale fragmentation of chromosomes and the acceptance of the opposed view of Raghavan and Venkatasubban and others.
5. Holttum's transference of the genus Zingiber to the tribe Hedychieae has been given cytological support on the following points:
a) the basic number in the genus Zingiber correlates with that of Kaempferia.
) the new tribe Alpinieae (which is infact Zingibereae without Zingiber) have consistently 48 chromosomes in their somatic complements.
6. It is suggested that the African representatives of Kaempferia should be given the status of genus; Cienkowskya on the following points:
a) the difference in floral morphology
) geographical separateness and
) the difference in the number and morphology of the chromosomes. By comparing the present and past findings, various lines of evolution of the chromosome complements within each group are discussed.
7. The basic number 11 is considered to be probably the original one for the Zingiberales as a whole, being present in Ravenala which is the most primitive member in the order. From this secondary basic numbers have arisen through evolution.

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Two new polyacetylene compounds (4, 6, 12)--acetoxy--isovaleryloxytetradeca-4, 6, 12-trien-, 10-diyn-14-ol (), and (4, 6, 12)--acetoxy--(-methylbutyryloxy)tetradeca-4, 6, 12-trien-, 10-diyn-14-ol () have been isolated along with (4, 6, 12)--acetoxy--senecioyloxytetradeca-4, 6, 12-trien-, 10-diyn-14-ol (A) from Atractylodes Rhizome (Karabyakujutu). The structures of these compounds were determined on the basis of their spectral data.

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Background

The differences in conditions of enteric-coated acid-labile drug release and absorption between healthy subjects in bioequivalence studies and gastrointestinal patients in clinical practice can lead to significant differences in gastric stability of original PPIs and generics. Thus, pathologic duodenogastric reflux (PDGR) and the pH increasing within PPIs administration still remain unaccounted for.

Methods

Two-stage modified comparative dissolution testing of original omeprazole (OO) and four generics (G

;;;4) was performed. At first, we moved drugs from solution with pH . (.±0.05) to pH 7.0 (7.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH 7 exposure time of resistance to PDGR for omeprazole is 4 minutes, i.. the active substance should not be released within 4 minutes at pH 7. The exposure at the second stage was conducted with pH 4 (4.0±0.05), that imitated gastric pH after PPI administration. And then we also moved drugs to pH 7 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH 7 solution at the first stage were different for OO and generics. For OO, these values were 4,7±0,7%; 41,4±

,0%; 62,±4,0%; 79,5±,9%; ,5±,9%; ,6±,9%; 80,6±4,4%; for Generic - 0; 49,±9,9%; , ±,%; ,4±,7%; , ±,%; 87,±,0%; 85,9±,%; for Generic - 0; 30,6±6,%; 66,7±,%; 76,4±7,4%; ,±5,%; 86,0±,7%; 84,6±,%: for Generic - 80,±,6%; ,5±,9%; , ±,%; ,±,7%; ,9±,%; ,±,0%; ,0±,4%; for Generic4 - ,5±,7%; 84,4±0,%; 84,±,%; , 9±0,9%; ,9±0,9%; ,9±0,9%; ,±,%, respectively.

An analysis of the omeprazole concentration in pH 7 solution at the second stage revealed the following parameters after the same time: for OO - 4,4±0,6%; 40, 5±

,0%; 62,±,0%; 80,0±,%; 85,4±,9%; ,±,4%; 80,9±,5%; for Generic - 0; 67,0±7,%; 89,7±,%; 91, 9±4,%; 89,±,6%; ,±,4%; 87,±,%; for Generic - 0; 42,±5,6%; 75,±7,%; ,0±6,0%; ,4±,%; , 6±,%; 87,9±,0%; for Generic4 - 85,5±0,5%; 85,6±0,5%; 84,7±0,9%; ,7±,0%; 84,4±0,%; 84,4±0,%; 84,±0,4%, respectively. Generic release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic

and Generic4 makes PDGR and inhibited gastric acid secretion due to PPIs administration the potential causes of decreased enteric-coated acid-labile drugs stability.

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  The distribution of sarcophytol-A in the Sarcophyton genus was investigated in seven samples belonging to S. glaucum ( samples), S. infundibulifurme ( samples), S. crassocaule ( sample) and S. trocheliophorum ( sample) that were collected on Ishigaki Island in Okinawa Prefecture. Sarcophytol-A was present in one sample each of S. glaucum and S. infundibulifurme. This study indicates that the composition of cembranoids in the Sarcophyton genus is not related with the respective species, but with the individual samples collected.

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Circuit techniques to enhance the linearity of input-voltage-to-current (V/I) conversion and to increase the output impedance of a current source by compensating for the low intrinsic gain of a transistor were introduced to realize a high-frequency operational transconductance amplifier (OTA) for a low supply voltage using sub-100-nm CMOS processes. Applying these techniques, a MOS 7th-order Gm- linear-phase low-pass filter (LPF) was realized using a 65nm CMOS process. A simplified biquad LPF that can serve as a component of a 7th-order LPF was newly developed by replacing OTAs with resistors. As a result, the -dB frequency bandwidth, group delay ripple, rd-order distortion, and rd-order input intercept point (IIP) were 200MHz, .%, ≤ -55dB with a 100MHz input, and +10.dBm, respectively, all with a ±0.Vp-p input signal at each input terminal in the pseudodifferential configuration. The LPF including an output buffer dissipated 60mW in the case of a .V supply. Wide spurious-free dynamic range (SFDR) characteristics were confirmed up to high frequencies.

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Autophagy is an intracellular degradation system regulating cellular homeostasis. The two ubiquitin-like modification systems named the Atg

system and the Atg12 system are essential for autophagy. Atg and Atg12 are ubiquitin-like proteins covalently conjugated with a phosphatidylethanolamine (PE) and Atg5, respectively, via enzymatic reactions. The Atg–PE conjugate binds to autophagic membranes and recruits various proteins through direct interaction, whereas the Atg12–Atg5 conjugate recognizes Atg, the enzyme for Atg, and facilitates Atg–PE conjugation by functioning as the enzyme. Although structural and biochemical analyses have well established the Atg-family interacting motif (AIM), studies on the interacting sequence for Atg12 are rare (only one example for human ATG12–ATG), thereby making it challenging to define a binding motif. Here we determined the crystal structure of the plant ATG12 as a complex with the ATG12-binding region of ATG and revealed that ATG12 recognizes the aspartic acid (Asp)–methionine (Met) motif in ATG via a hydrophobic pocket and a basic residue, which we confirmed critical for the complex formation by mutational analysis. This recognition mode is similar to that reported between human ATG12 and ATG, suggesting that the Asp–Met sequence is a conserved Atg12-interacting motif (AIM12). These data suggest that AIM12 mediates - interaction during Atg lipidation and provide structural basis for developing chemicals that regulate autophagy by targeting Atg12-family proteins.

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The correction factor (η_ie) for the ultimate bearing capacity of a footing placed adjacent to a slope, taking into account the combined effect of horizontal and vertical seismic loads, represented by horizontal and vertical seismic coefficients, k_h and k_v, respectively, was derived using a modified Janbu's slice method. The influence of slope angles ‘α’ on the values of ‘η_ie’ are studied here. It was found that the values of η_ie can be expressed as an exponential function of ‘k_h/(-k_v)’ and ‘α’, with a measurable interdependency between ‘α’ and ‘η_ie’. The influence of ‘α’ on the value of ‘η_ie’ increases as the input value of ‘k_h/(-k_v)’ increases. Equations derived based on the analytical results are proposed to account for this effect. Based on the analyses of 11 near-fault seismographers obtained in the 1999 Chi-Chi earthquake in Taiwan, a ratio between the vertical and the horizontal seismic coefficients, λ, of between ±0.25 is suggested for including the combined effect of vertical and horizontal seismic forces in evaluating the seismic bearing capacity of footings located in near-fault areas.

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At present, analytical or empirical formula for seismic bearing capacity of footings adjacent to slopes is not available. This study uses a pseudo-static-based approach in conjunction with rigorous Janbu's slice method to derive analytical values of seismic bearing capacity factors (N_γ) and correction factors for the effects of inertia of soil mass and load inclinations for a rigid footing adjacent to cohesionless slopes. It is shown that both the bearing capacity factors (N_γ) and the correction factors for the seismic bearing capacity of footings placed on level ground derived herein are comparable with those reported in the literature. Empirical equations regarding the effects of slope angles and load inclinations, expressed using generalized forms of those proposed in the literature, are also derived. It is also found that the empirical equations derived in the present study provide values of correction factors in good agreements with the analytical ones, indicating the validity of using these empirical equations for assessing the bearing capacity of rigid footings situated on the slope subjected to pseudo-static seismic loading.

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