Selection of Color-Changing and Intensity-Increasing Fluorogenic Probe as Protein-Specific Indicator Obtained via the 10BASEd-T

To obtain a molecular probe for specific protein detection, we have synthesized fluorogenic probe library of vastdiversity on bacteriophage T7 via the gp10 based-thioetherificaion (10BASEd-T). A remarkable color-changing and turning-on probewas selected from the library, and its physicochemical properties upon target-specific binding were obtained. Combination analysesof fluorescence emission titration, isothermal titration calorimetry (ITC), and quantitative saturation-transfer difference (STD) NMRmeasurements followed by in silico docking simulation, rationalized most plausible geometry of the ligand-protein interaction

Medium-firm drug-candidate library of cryptand-like structures on T7: Design and selection of strong binder for Hsp90

We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 10^9 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (K_D = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD)

A liquid crystalline phase in spermidine-condensed DNA

Over a large range of salt and spermidine concentrations, short DNA fragments precipitated by spermidine (a polyamine) sediment in a pellet from a dilute isotropic supernatant. We report here that the DNA-condensed phase consists of a cholesteric liquid crystal in equilibrium with a more concentrated phase. These results are discussed according to Flory's theory for the ordering of rigid polymers. The liquid crystal described here corresponds to an ordering in the presence of attractive interactions, in contrast with classical liquid crystalline DNA. Polyamines are often used in vitro to study the functional properties of DNA. We suggest that the existence of a liquid crystalline state in spermidine-condensed DNA is relevant to these studies

Output Prediction Attacks on Block Ciphers using Deep Learning

Cryptanalysis of symmetric-key ciphers, e.g., linear/differential cryptanalysis, requires an adversary to know the internal structures of the target ciphers. On the other hand, deep learning-based cryptanalysis has attracted significant attention because the adversary is not assumed to have knowledge about the target ciphers with the exception of the algorithm interfaces. Such cryptanalysis in a blackbox setting is extremely strong; thus, we must design symmetric-key ciphers that are secure against deep learning-based cryptanalysis. However, almost previous attacks do not clarify what features or internal structures affect success probabilities. Although Benamira et al. (Eurocrypt 2021) and Chen et al. (ePrint 2021) analyzed Gohr’s results (CRYPTO 2019), they did not find any deep learning specific characteristic where it affects the success probabilities of deep learning-based attacks but does not affect those of linear/differential cryptanalysis. Therefore, it is difficult to employ the results of such cryptanalysis to design deep learning-resistant symmetric-key ciphers. In this paper, we propose deep learning-based output prediction attacks in a blackbox setting. As preliminary experiments, we first focus on two toy SPN block ciphers (small PRESENT-[4] and small AES-[4]) and one toy Feistel block cipher (small TWINE-[4]). Due to its small internal structures with a block size of 16 bits, we can construct deep learning models by employing the maximum number of plaintext/ciphertext pairs, and we can precisely calculate the rounds in which full diffusion occurs. Next, based on the preliminary experiments, we explore whether the evaluation results obtained by our attacks against three toy block ciphers can be applied to block ciphers with large block sizes, e.g., 32 and 64 bits. As a result, we demonstrate the following results, specifically for the SPN block ciphers: First, our attacks work against a similar number of rounds that the linear/differential attacks can be successful. Next, our attacks realize output predictions (precisely ciphertext prediction and plaintext recovery) that are much stronger than distinguishing attacks. Then, swapping or replacing the internal components of the target block ciphers affects the average success probabilities of the proposed attacks. It is particularly worth noting that this is a deep learning specific characteristic because swapping/replacing does not affect the average success probabilities of the linear/differential attacks. Finally, by analyzing the influence of the differences in the characteristics of three S-boxes (i.e., the original PRESENT S-box and two known weak S-boxes) on deep learning specific characteristics, we clarify that the resistance of the target ciphers to differential/linear attacks can affect the success probability of deep learning-based attacks. We also confirm whether the proposed attacks work on the Feistel block cipher. We expect that our results will be an important stepping stone in the design of deep learning-resistant symmetric-key ciphers

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use

How did rehabilitation professionals act when faced with the Great East Japan earthquake and disaster? Descriptive epidemiology of disability and an interim report of the relief activities of the ten Rehabilitation-Related Organizations.

Objective: Inter-organizational coordination is important for rehabilitation disaster relief. The 2011 Great East Japan Earthquake and Disaster was unprecedented, being geographically widespread and multifaceted. Faced with the crisis, rehabilitation professionals established the 10 Rehabilitation- Related Organizations of Rehabilitation Support Service (10-RRO). The objectives of this paper are to provide descriptive epidemiology and assess the activities of 10- RRO. Design: Descriptive. Methods: Epidemiological data on disability were collected, mainly from official sources. Relief activities were reviewed from daily reports, and the preparedness, initial response and functioning of 10-RRO were assessed with a questionnaire directed at 36 executives of individual organizations. Results: The disaster was characterized by a very low ratio of injuries to death of 0.372, and an odds ratio of deaths among disabled persons of 2.32. 10-RRO provided relief activities at 3 shelters. The total number of dispatch days ranged from 107 to 146, and the cumulative number of professionals and evacuees served was 1,202 and 7,300, respectively. Support activities included prevention of immobilization, daily life support, environmental improvement and transition to temporary housing. The questionnaire survey revealed poor preparedness, satisfactory initial response and support activities, and problems of data collection and advocacy. Conclusion: The disaster was characterized by minimal trauma and a great need for preventing immobilization. This first collaborative endeavour was successful

Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

BACKGROUND: Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI) patients. CASE PRESENTATION: A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1 – 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 – 1.8). Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology: Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by normal urothelial cells. A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. CONCLUSION: This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs