gebhart/patrepeval huggingface dataset:
Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding (2017)

Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity. In rabbit immunizations with native-like trimers of the 327c isolate, improved trimers suppress elicitation of V3-directed and tier-1 neutralizing antibodies and induce robust autologous tier-2 neutralization, unlike a first-generation trimer. The improved native-like trimers from diverse HIV isolates, and the design methods, have promise to assist in the development of a HIV vaccine.
WeBuild (2017)

Physical construction and assembly tasks are often carried out by groups of collocated workers, and they can be difficult to coordinate. Group members must spend time deciding how to split up the task, how to assign subtasks to each other, and in what order subtasks should be completed. Informed by an observational study examining group coordination challenges, we built a task distribution system called WeBuild. Our custom algorithm dynamically assigns subtasks to workers in a group, taking into account factors such as the dependencies between subtasks and the skills of each group member. Each worker views personalized step-by-step instructions on a mobile phone, while a dashboard visualizes the entire process. An initial study found that WeBuild reduced the start-up time needed to coordinate and begin a task, and provides direction for future research to build on toward improving group efficiency and coordination for complex tasks.
Arachidonic Acid Plays a Role in Rat Vomeronasal Signal Transduction (2002)

Sensory neurons of the vomeronasal organ (VNO) detect volatile chemicals that are released by conspecific animals and convey information about social and reproductive behavior. The signal transduction pathway in vomeronasal receptor neurons (VRNs) is not known in detail, but is believed to be distinct from that of the sensory neurons of the main olfactory system. Many of the identified olfactory transduction components are not expressed by VRNs. Using Ca2+ imaging and electrophysiological recordings, we investigated the signal transduction pathway of urine perception and the possible role of polyunsaturated fatty acids (PUFAs) as intracellular messengers in freshly dissociated rat VNO neurons. We found that application of urine induced a transient increase in intracellular Ca2+ that was dependent on the activity of phospholipase C and diacylglycerol (DAG) lipase. The Ca2+ transient was not dependent on depletion of intracellular Ca2+ stores but was dependent on the presence of extracellular Ca2+. Furthermore, the urine response was not sensitive to modulators of adenylate cyclase and inhibitors of inositol 1,4,5-trisphosphate receptors. Application of PUFAs (linolenic acid and arachidonic acid, synthesized in living cells from DAG) also elicited Ca2+ transients in fura 2 measurements and inward currents in whole-cell voltage-clamp recordings. Pharmacological inhibition of lipoxygenase and cyclooxygenase induced a transient increase in intracellular Ca2+, possibly by increasing the endogenous level of PUFAs, leading to activation of transduction channels. These data provide evidence for a role of PUFAs in rat vomeronasal signal transduction.
Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome†‡ (2018)

The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE-II criteria, and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
Stepwise Adsorption of Alkoxy‐Pyrene Derivatives onto a Lamellar, Non‐Porous Naphthalenediimide‐Template on HOPG (2020)

The development of new strategies for the preparation of multicomponent supramolecular assemblies is a major challenge on the road to complex functional molecular systems. Here we present the use of a non-porous self-assembled monolayer from uC<sub>33</sub> -NDI-uC<sub>33</sub> , a naphthalenediimide symmetrically functionalized with unsaturated 33 carbon-atom-chains, to prepare bicomponent supramolecular surface systems with a series of alkoxy-pyrene (PyrOR) derivatives at the liquid/HOPG interface. While previous attempts at directly depositing many of these PyrOR units at the liquid/HOPG interface failed, the multicomponent approach through the uC<sub>33</sub> -NDI-uC<sub>33</sub> template enabled control over molecular interactions and facilitated adsorption. The PyrOR deposition restructured the initial uC<sub>33</sub> -NDI-uC<sub>33</sub> monolayer, causing an expansion in two dimensions to accommodate the guests. As far as we know, this represents the first example of a non-porous or non-metal complex-bearing monolayer that allows the stepwise formation of multicomponent supramolecular architectures on surfaces.
Durch rotes Licht kontrollierte Protein‐RNA‐Vernetzung mit einem genetisch kodierten Furan (2013)

Ein Komplex ist Voraussetzung: Eine Protein-RNA-Vernetzungsgruppe wurde genetisch kodiert, die durch Bestrahlung mit rotem Licht, das hohe Eindringtiefen in biologischen Proben aufweist, aktiviert werden kann. Dieser Ansatz ermöglicht die Kartierung von transienten Protein-RNA-Wechselwirkungen in komplexen Proben mit räumlicher und zeitlicher Auflösung sowie das Design von Peptid- und Protein-basierten Therapeutika mit chemischen Gefechtsköpfen für die RNA-gerichtete photodynamische Therapie. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Distinct effects of disease-associated TREM2 R47H/+ and T66M mutations on iPSC-derived microglia (2022)

Abstract Genetic findings have highlighted key roles for microglia in the pathology of neurodegenerative conditions such as Alzheimer’s disease (AD). Distinct mutations in the microglial protein TREM2 (triggering receptor expressed on myeloid cells 2) are associated with different forms of neurodegeneration in humans; R47H/+ mutations increase AD risk, while loss-of-function mutations such as TREM2 T66M result in more severe forms of neurodegeneration. We employed gene editing and stem cell models to gain insight into the effects of these mutations on human iPSC-derived microglia. We found divergent effects of TREM2 R47H/+ and T66M mutations on gene expression, with R47H/+ cells exhibiting a pro-inflammatory gene expression signature. Both the TREM2 R47H/+ and T66M mutations caused similar impairments in microglial movement and the uptake of multiple substrates, while R47H/+ microglia were hyper-responsive to inflammatory stimuli, consistent with their gene expression signature. We developed an in vitro laser-induced injury model in neuron-microglia co-cultures, finding an impaired injury response by TREM2 R47H/+ microglia. Furthermore, in xenotransplantation experiments, mouse brains transplanted with TREM2 R47H/+ microglia exhibited reduced synaptic density. Consistently, we observed upregulation of multiple complement cascade components in TREM2 R47H/+ microglia, suggesting that inappropriate synaptic pruning may underlie the effect. Thus, these findings identify shared and distinct effects of these two TREM2 mutations on microglial gene expression and function. While the TREM2 T66M mutation impairs microglial movement and uptake processes, the TREM2 R47H/+ mutation additionally confers multiple potentially detrimental effects on human microglia, likely to underlie its association with AD.
Efficient and Convenient Synthetic Routes for Sitagliptin Impurities (2018)

Abstract New efficient and convenient approaches have been devised for the synthesis of sitagliptin impurities. As a part of impurity profile study of an antidiabetic drug substance sitagliptin 1 , we encountered with six process related impurities. These impurities were detected by utilizing simple techniques such as high performance liquid chromatography (HPLC) and liquid chromatography ‐ mass spectrometry (LC–MS). All these impurities were synthesized and their presence in the sitagliptin sample was confirmed by co‐injection and matching the retention time with spiked impurities. The formation and control of these impurities during sitagliptin manufacture and synthesis of these impurities is discussed in detail. Synthesis of these impurities was accomplished by utilizing readily accessible starting materials, simple, convenient and concise reaction sequence.
The effect of calorie restriction on the presence of apoptotic ovarian cells in normal wild type mice and low-plasma-IGF-1 Laron dwarf mice (2013)

Morphological and histochemical analysis revealed a younger biological age of the ovaries in 2-year-old WT littermates and GHR-KO female mice on CR compared with animals fed AL.
Interview (2011)

Dr Clint Schow (right) and Dr Alexander Rylyakov (left) from IBM T. J. Watson Research Center in the US talk about their Letter '30-Gbit/s, 850-nm, VCSEL-based optical link' on page 1035.
Zero Trust Architecture Empowered Attack Detection Framework to Secure 6G Edge Computing (2023)

Recent advances in edge computing and its imminent adoption in Sixth Generation (6G) wireless networks have led to a propitious paradigm defined as 6G edge computing. However, due to the communication mode and network virtualization of the 6G architecture, 6G edge computing presents several security concerns, including attack monitoring and detection. In this article, we present a new and robust Zero Trust Architecture (ZTA) empowered intrusion detection framework to protect 6G edge computing from network attacks. The proposed detection framework executes detection techniques based on security rules and machine learning algorithms as well as detection strategies based on a standalone and collaborative process with the goal to harden the security and hence to detect accurately the attacks. Furthermore, we propose a dynamic ZTA based on a non-cooperative game to harden further the security of 6G edge computing networks, with consideration of detection accuracy in terms of false positives and false negatives, and network cost as a computational overhead.
American sign language recognition in game development for deaf children (2006)

CopyCat is an American Sign Language (ASL) game, which uses gesture recognition technology to help young deaf children practice ASL skills. We describe a brief history of the game, an overview of recent user studies, and the results of recent work on the problem of continuous, user-independent sign language recognition in classroom settings. Our database of signing samples was collected from user studies of deaf children playing aWizard of Oz version of the game at the Atlanta Area School for the Deaf (AASD). Our data set is characterized by disfluencies inherent in continuous signing, varied user characteristics including clothing and skin tones, and illumination changes in the classroom. The dataset consisted of 541 phrase samples and 1,959 individual sign samples of five children signing game phrases from a 22 word vocabulary. Our recognition approach uses color histogram adaptation for robust hand segmentation and tracking. The children wear small colored gloves with wireless accelerometers mounted on the back of their wrists. The hand shape information is combined with accelerometer data and used to train hidden Markov models for recognition. We evaluated our approach by using leave-one-out validation; this technique iterates through each child, training on data from four children and testing on the remaining child's data. We achieved average word accuracies per child ranging from 91.75% to 73.73% for the user-independent models.
A pilot study of machine learning of resting-state EEG and depression in Parkinson’s disease (2022)

Our results suggest that resting-state EEG power spectral analysis has the potential to distinguish depression in PD accurately. We demonstrated the efficacy of the LEAPD algorithm in identifying PD patients with depression from PD patients without depression and controls with depression. Our data provide insight into cortical mechanisms of depression and could lead to novel neurophysiological markers for non-motor symptoms of PD.
2 GHz<tex>$rm Q$</tex>-Enhanced Active Filter With Low Passband Distortion and High Dynamic Range (2006)

A tunable Q-enhanced filter with low passband distortion is presented. The Q of the on-chip spiral inductors that form the filter resonators is enhanced by using a cross-coupled differential pair which is degenerated by a second LC tank. This technique allows for frequency dependent compensation of inductor losses and ensures that the Q-enhanced LC resonators have a frequency behaviour close to the ideal in the passband of the filter. The circuit allows DC voltage control of Q-enhancement. The filter centered at 2.0 GHz with a 130 MHz bandwidth is tunable in frequency by 3%, exhibits a -6.6 dBm 1-dB compression point and a 15 dB noise figure while consuming 17 mW of DC power. The circuit was fabricated in 0.18-mum CMOS and the performance was verified experimentally
Methylation Interference Assay (2007)

INTRODUCTIONMethylation interference (and methylation protection) is the major technique for studying the interaction of proteins with major-groove guanines, although it also detects adenines in the minor groove and cytosines in single-stranded DNA. It is one of the highest-resolution methods for measuring the bases involved in sequence-specific recognition by proteins. A (32)P-end-labeled DNA containing a recognition site is methylated (on average once per DNA molecule) by dimethyl sulfate (DMS) and then protein is allowed to bind. Certain methylation modifications prevent the protein from binding because they are at positions where the protein comes into close proximity with the DNA. Most modifications, however, have no effect on binding. The bound and unbound DNA molecules are separated using the electrophoretic mobility shift assay (or filter binding, immunoprecipitation, or any other suitable technique). The unbound fraction will be enriched in DNA molecules containing modifications at positions that interfere with protein binding. In contrast, the bound fraction will contain modifications that do not interfere with binding of the protein. Methylation weakens the nucleotide and makes it susceptible to piperidine-induced depurination. This leads, in turn, to scission of the DNA backbone. The cleaved fragments are fractionated on a sequencing gel alongside chemical sequencing ladders to identify the affected positions.
Overexpression of the IbMYB1 gene in an orange‐fleshed sweet potato cultivar produces a dual‐pigmented transgenic sweet potato with improved antioxidant activity (2014)

The R2R3-type protein IbMYB1 is a key regulator of anthocyanin biosynthesis in the storage roots of sweet potato [Ipomoea batatas (L.) Lam]. Previously, we demonstrated that IbMYB1 expression stimulated anthocyanin pigmentation in tobacco leaves and Arabidopsis. Here, we generated dual-pigmented transgenic sweet potato plants that accumulated high levels of both anthocyanins and carotenoids in a single sweet potato storage root. An orange-fleshed cultivar with high carotenoid levels was transformed with the IbMYB1 gene under the control of either the storage root-specific sporamin 1 (SPO1) promoter or the oxidative stress-inducible peroxidase anionic 2 (SWPA2) promoter. The SPO1-MYB transgenic lines exhibited higher anthocyanin levels in storage roots than empty vector control (EV) or SWPA2-MYB plants, but carotenoid content was unchanged. SWPA2-MYB transgenic lines exhibited higher levels of both anthocyanin and carotenoids than EV plants. Analysis of hydrolyzed anthocyanin extracts indicated that cyanidin and peonidin predominated in both overexpression lines. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that IbMYB1 expression in both IbMYB1 transgenic lines strongly induced the upregulation of several genes in the anthocyanin biosynthetic pathway, whereas the expression of carotenoid biosynthetic pathway genes varied between transgenic lines. Increased anthocyanin levels in transgenic plants also promoted the elevation of proanthocyanidin and total phenolic levels in fresh storage roots. Consequently, all IbMYB1 transgenic plants displayed much higher antioxidant activities than EV plants. In field cultivations, storage root yields varied between the transgenic lines. Taken together, our results indicate that overexpression of IbMYB1 is a highly promising strategy for the generation of transgenic plants with enhanced antioxidant capacity.
Calpain Protease-dependent Post-translational Regulation of Cyclin D3 (2015)

칼슘 의존적으로 활성화되는 neutral protease calpain에 의한 단백질 분해는 세포의 성장을 조절하는데 중요한 단백질들의 역할에 매우 중요한 역할을 한다. Cyclin의 분해는 세포주기의 진행을 위한 필연적인 과정이다. D-type cyclins는 외부자극이나 신호에 의하여 세포주기의 G1 초기에 합성이 된 후 cyclin-dependent kinases (cdk4 및 cdk6)와의 결합하여 세포주기 S기 진입을 촉진하는 역할을 한다. 본 연구에서는 cyclin D3 단백질이 calpain protease에 의하여 번역 후 수준에서 조절 받고 있음을 제시하였다. 본 실험의 조건에서 lovastatin과 actinomycin D가 처리된 PC-3-M 전립선 암세포에서 cyclin D3 단백질의 발현이 완전히 사라졌지만, calpain inhibitor인 LLnL의 처리에 의하여 정상 수준으로 회복되었음을 알 수 있었다. 그러나 26S proteasome의 선택적 억제제인 lactacystin, lysosome 억제제인 ammonium chloride 및 chloroquine, serine protease 억제제인 PMSF는 동일 조건에서 lovastatin과 actinomycin D 처리에 의한 cyclin D3 단백질의 발현저하를 억제하지는 못하였다. In vitro 조건에서 순수 분리된 calpain은 cyclin D3 단백질을 칼슘 농도 의존적으로 분해하였으며, cyclin D3 단백질의 반감기는 LLnL 처리에 의하여 매우 유의적으로 증가되었다. 또한 calpain 저해인자인 calpastatin의 과발현은 PC-3-M 세포에서 뿐만 아니라 NIH 3T3 섬유아세포에서도 cyclin D3 단백질의 반감기 및 안전성을 증대시켰다. 이러한 결과는 cyclin D3 단백질이 칼슘에 의해 활성화 되는 protease calpain에 의해 조절됨을 보여주는 것이다. Cyclin D is a member of the cyclin protein family, which plays a critical role as a core member of the mammalian cell cycle machinery. D-type cyclins (D1, D2, and D3) bind to and activate the cyclin-dependent kinases 4 and 6, which can then phosphorylate the retinoblastoma tumor suppressor gene products. This phosphorylation in turn leads to release or derepression of E2F transcription factors that promote progression from the G1 to S phase of the cell cycle. Among the D-type cyclins, cyclin D3 encoded by the CCND3 gene is one of the least well studied. In the present study, we have investigated the biochemistry of the proteolytic mechanism that leads to loss of cyclin D3 protein. Treatment of human prostate carcinoma PC-3-M cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. Additionally, using inhibitors for various proteolytic systems, we show that degradation of cyclin D3 protein involves the <TEX>$Ca^{2+}$</TEX>-activated neutral protease calpain. Moreover, the half-life of cyclin D3 protein half-life increased by at least 10-fold in PC-3M cells in response to the calpain inhibitor. We have also demonstrated that the transient expression of the calpain inhibitor calpastatin increased cyclin D3 protein in serum-starved NIH 3T3 cells. These data suggested that the function of cyclin D3 is regulated by <TEX>$Ca^{2+}$</TEX>-dependent protease calpain.
Downstream Considerations of Fusion Clad Casting (2009)

Fusion casting has been commercially available for over 3 years. Although there are many interesting points to casting, there are several downstream considerations such as scalping, preheat and rolling. Quality rolled clad sheet needs to have a consistent clad thickness. Appropriately varying the geometry of the clad layer during the transient portions of casting results in consistent clad thickness from head to butt. Controlling the edge wipe during rolling off does the same from edge to edge. The severity of edge wipe off can be predicted from relative flow stresses at rolling temperatures and guides the choice of alloy combinations.
The Effect of a&lt;i&gt; Lactobacillus&lt;/i&gt;-Based Probiotic for the Control of Necrotic Enteritis in Broilers (2013)

Necrotic Enteritis (NE) caused by Clostridium perfringens (CP) in poultry is probably the most important bacterial disease in terms of economic implications. The disease is multi-factorial and is invariably associated with predisposing factors. The present study investigated the effect of a commercially available Lactobacillus-based probiotic (FM-B11) for the control of necrotic enteritis in broiler chickens. In experiment 1, one-day-of-hatch broiler chicks were randomly allocated to the following treatment groups: 1) Non-challenged (NC); 2) Challenged (C); 3) Challenged + probiotic (C+ FM-B11). Prior to placement, chicks in groups 2 and 3 received 0.25 mL of Salmonella typhimurium (ST) containing 105 cfu of viable cells by oral gavage. At 14, 15 and 16 days of age, all chicks in group 3 were treated with FM-B11 in the drinking water at a concentration of 106 cfu/ml. At 21d of age, all chicks in groups 2 and 3, were individually challenged with 5 × 104 sporulated oocysts of E. maxima by oral gavage. At 26d of age, all chicks in groups 2 and 3, were individually challenged with 108 cfu CP; body weight (BW) was recorded prior to challenge. The experiment was terminated at 29 days of age and the following parameters were evaluated: NE-associated mortality, CP lesion scores, CP concentrations in ileum, BW, and body weight gain (BWG). Chicks treated with FM-B11 had significantly (P 0.05) difference in lesion score between C and C + FM-B11, group C + FM-B11 had significantly (P Lactobacillus-based probiotic FM-B11 was able to reduce the severities of NE, as a secondary bacterial infection, in an experimental NE challenge model; as well as, in a commercial field outbreak of NE.