Crystallization of Adenylylsulfate Reductase from Desulfovibrio gigas: A Strategy Based on Controlled Protein Oligomerization

Adenylylsulfate reductase (adenosine 5′-phosphosulfate reductase, APS reductase or APSR, E.C.1.8.99.2) catalyzes the conversion of APS to sulfite in dissimilatory sulfate reduction. APSR was isolated and purified directly from massive anaerobically grown Desulfovibrio gigas, a strict anaerobe, for structure and function investigation. Oligomerization of APSR to form dimers–α_2β_2, tetramers–α_4β_4, hexamers–α_6β_6, and larger oligomers was observed during purification of the protein. Dynamic light scattering and ultracentrifugation revealed that the addition of adenosine monophosphate (AMP) or adenosine 5′-phosphosulfate (APS) disrupts the oligomerization, indicating that AMP or APS binding to the APSR dissociates the inactive hexamers into functional dimers. Treatment of APSR with β-mercaptoethanol decreased the enzyme size from a hexamer to a dimer, probably by disrupting the disulfide Cys156—Cys162 toward the C-terminus of the β-subunit. Alignment of the APSR sequences from D. gigas and A. fulgidus revealed the largest differences in this region of the β-subunit, with the D. gigas APSR containing 16 additional amino acids with the Cys156—Cys162 disulfide. Studies in a pH gradient showed that the diameter of the APSR decreased progressively with acidic pH. To crystallize the APSR for structure determination, we optimized conditions to generate a homogeneous and stable form of APSR by combining dynamic light scattering, ultracentrifugation, and electron paramagnetic resonance methods to analyze the various oligomeric states of the enzyme in varied environments

Implementation of the CMOS MEMS Condenser Microphone with Corrugated Metal Diaphragm and Silicon Back-Plate

This study reports a CMOS-MEMS condenser microphone implemented using the standard thin film stacking of 0.35 μm UMC CMOS 3.3/5.0 V logic process, and followed by post-CMOS micromachining steps without introducing any special materials. The corrugated diaphragm for the microphone is designed and implemented using the metal layer to reduce the influence of thin film residual stresses. Moreover, a silicon substrate is employed to increase the stiffness of the back-plate. Measurements show the sensitivity of microphone is −42 ± 3 dBV/Pa at 1 kHz (the reference sound-level is 94 dB) under 6 V pumping voltage, the frequency response is 100 Hz–10 kHz, and the S/N ratio >55 dB. It also has low power consumption of less than 200 μA, and low distortion of less than 1% (referred to 100 dB)

FishEye8K: A Benchmark and Dataset for Fisheye Camera Object Detection

With the advance of AI, road object detection has been a prominent topic in computer vision, mostly using perspective cameras. Fisheye lens provides omnidirectional wide coverage for using fewer cameras to monitor road intersections, however with view distortions. To our knowledge, there is no existing open dataset prepared for traffic surveillance on fisheye cameras. This paper introduces an open FishEye8K benchmark dataset for road object detection tasks, which comprises 157K bounding boxes across five classes (Pedestrian, Bike, Car, Bus, and Truck). In addition, we present benchmark results of State-of-The-Art (SoTA) models, including variations of YOLOv5, YOLOR, YOLO7, and YOLOv8. The dataset comprises 8,000 images recorded in 22 videos using 18 fisheye cameras for traffic monitoring in Hsinchu, Taiwan, at resolutions of 1080$\times$1080 and 1280$\times$1280. The data annotation and validation process were arduous and time-consuming, due to the ultra-wide panoramic and hemispherical fisheye camera images with large distortion and numerous road participants, particularly people riding scooters. To avoid bias, frames from a particular camera were assigned to either the training or test sets, maintaining a ratio of about 70:30 for both the number of images and bounding boxes in each class. Experimental results show that YOLOv8 and YOLOR outperform on input sizes 640$\times$640 and 1280$\times$1280, respectively. The dataset will be available on GitHub with PASCAL VOC, MS COCO, and YOLO annotation formats. The FishEye8K benchmark will provide significant contributions to the fisheye video analytics and smart city applications.Comment: CVPR Workshops 202

Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan

<p>Abstract</p> <p>Background</p> <p>The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.</p> <p>Methods</p> <p>We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.</p> <p>Results</p> <p>There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.</p> <p>Conclusions</p> <p>This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.</p

Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity

<p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.</p> <p>Methods</p> <p>We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.</p> <p>Results</p> <p>The 50% effective inhibitory concentration (IC₅₀) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.</p> <p>Conclusions</p> <p>To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.</p

Comparison of Acute Lobar Nephronia and Acute Pyelonephritis in Children: A Single-Center Clinical Analysis in Southern Taiwan

BackgroundPatients with acute lobar nephronia (ALN) require a longer duration of antimicrobial treatment than those with acute pyelonephritis (APN), and ALN is associated with renal scarring. The aim of this study was to provide an understanding of ALN by comparing the clinical features of pediatric patients with ALN and APN.MethodsWe enrolled all of the patients with ALN (confirmed by computed tomography) admitted to our hospital from 1999 to 2012 in the ALN group. In addition, each patient diagnosed with APN who was matched for sex, age, and admission date to each ALN patient was enrolled in the APN group. The medical charts of patients in these two groups were retrospectively reviewed and analyzed for comparison.ResultsThe fever duration after hospitalization in the ALN group and the APN group were 4.85 ± 2.33 days and 2.30 ± 1.47 days respectively. The microbiological distributions and the majority of susceptibilities were similar in the ALN and APN groups. The majority of clinical manifestations are nonspecific and unreliable for the differentiation of ALN and APN. The patients with ALN were febrile for longer after antimicrobial treatment, had more nausea/vomiting symptoms, higher neutrophil count, bandemia, and C-reactive protein (CRP) levels, and lower platelet count (all p < 0.05). In multivariate analysis, initial CRP levels, nausea/vomiting symptoms, and fever duration after admission were independent variables with statistical significance to predict ALN. Severe nephromegaly occurred significantly more in the ALN group than in the APN group (p = 0.022).ConclusionThe majority of clinical manifestations, laboratory findings, and microbiological features are similar between patients with ALN and APN. Clinicians should keep a high index of suspicion regarding ALN, particularly for those with ultrasonographic nephromegaly, initial higher CRP, nausea/vomiting, and fever for > 5 days after antimicrobial treatment

The Taiwan Birth Panel Study: a prospective cohort study for environmentally- related child health

<p>Abstract</p> <p>Background</p> <p>The Taiwan Birth Panel Study (TBPS) is a prospective follow-up study to investigate the development of child health and disease in relation to in-utero and/or early childhood environmental exposures. The rationale behind the establishment of such a cohort includes the magnitude of potential environmental exposures, the timing of exposure window, fatal and children's susceptibility to toxicants, early exposure delayed effects, and low-level or unknown neurodevelopmental toxicants.</p> <p>Methods</p> <p>A total of 486 mother-infant paired was enrolled from April 2004 to January 2005 in this study. Maternal blood before delivery, placenta and umbilical cord blood at birth, and mothers' urine after delivery were collected. The follow-up was scheduled at birth, 4, 6 months, and 1, 2, 3 and 5 years. The children's blood, urine, hair, and saliva were collected at 2 years of age and children's urine was collected at 5 years of age as well. The study has been approved by the ethical committee of National Taiwan University Hospital. All the subjects signed the inform consent on entering the study and each of the follow up.</p> <p>Results</p> <p>Through this prospective birth cohort, the main health outcomes were focused on child growth, neurodevelopment, behaviour problem and atopic diseases. We investigated the main prenatal and postnatal factors including smoking, heavy metals, perfluorinated chemicals, and non-persistent pesticides under the consideration of interaction of the environment and genes.</p> <p>Conclusions</p> <p>This cohort study bridges knowledge gaps and answers unsolved issues in the low-level, prenatal or postnatal, and multiple exposures, genetic effect modification, and the initiation and progression of "environmentally-related childhood diseases."</p

Effect of Acupressure and Trigger Points in Treating Headache: A Randomized Controlled Trial

Abstract: The efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To address this, a randomized, controlled clinical trial was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight patients suffering chronic headache were randomly assigned to the acupressure group (n = 14) or the muscle relaxant medication group (n = 14). Outcome measures regarding self-appraised pain scores (measured on a visual analogue scale; VAS) and ratings of how headaches affected life quality were recorded at baseline, 1 month after treatment, and at a 6-month follow-up. Pain areas were recorded in order to establish trigger points. Results showed that mean scores on the VAS at post-treatment assessment were significantly lower in the acupressure group (32.9 ± 26.0) than in the muscle relaxant medication group (55.7 ± 28.7) (p = 0.047). The superiority of acupressure over muscle relaxant medication remained at 6-month follow-up assessments (p = 0.002). The quality of life ratings related to headache showed similar differences between the two groups in the post treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and GB5 were used most commonly for etiological assessment. In conclusion, our study suggests that 1 month of acupressure treatment is more effective in reducing chronic headache than 1 month of muscle relaxant treatment, and that the effect remains 6 months after treatment. Trigger points help demonstrate the treatment technique recommended if a larger-scale study is conducted in the future