gebhart/patrepeval huggingface dataset:
Supraphysiological testosterone induces ferroptosis and activates NF-kappaB mediated immune pathways in prostate cancer through nucleophagy (2020)

Abstract The discovery that androgens play an important role in the progression of prostate cancer (PCa) has led to the development of androgen deprivation therapy as a first line of treatment against PCa. However, paradoxical growth inhibition has been observed, both experimentally and clinically, in a subset of PCa upon administration of supraphysiological levels of testosterone (SupraT). Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive PCa cells. This is initiated by induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activates nucleic acid sensors that converge on NF-kappaB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT results in increased migration of cytotoxic immune cells to tumor beds of animal xenografts and patient tumors. Collectively, our findings indicate that SupraT may inhibit a subset of PCa by activating nucleic acid sensors and downstream immune signaling.
A sample-to-answer COVID-19 diagnostic device based on immiscible filtration and CRISPR-Cas12a-assisted detection (2022)

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic and disparities of vaccination coverage in low-and middle-income countries, it is vital to adopt a widespread testing and screening programme, combined with contact tracing, to monitor and effectively control the infection dispersion in areas where medical resources are limited. This work presents a lab-on-a-chip device, namely 'IFAST-LAMP-CRISPR', as an affordable, rapid and high-precision molecular diagnostic means for detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The herein proposed 'sample-to-answer' platform integrates RNA extraction, amplification and molecular detection with lateral flow readout in one device. The microscale dimensions of the device containing immiscible liquids, coupled with the use of silica paramagnetic beads and guanidine hydrochloride, streamline sample preparation (including RNA extraction, concentration and purification) in 15 min with minimal hands-on steps. The pre-amplification in combination with CRISPR-Cas12a detection assays targeting the nucleoprotein (N) gene achieved visual identification of ≥ 470 copies mL<sup>-1</sup> genomic SARS-CoV-2 samples in 45 min. On-chip assays showed the ability to isolate and detect SARS-CoV-2 RNA from 100 genome copies mL<sup>-1</sup> of replication-deficient viral particles in 1 h. This simple, affordable and integrated platform demonstrated a visual, faster, and yet specificity- and sensitivity-comparable alternative to the costly gold-standard reverse transcription-polymerase chain reaction (RT-PCR) assay, requiring only a simple heating source. Initial testing illustrates the platform viability both on nasopharyngeal swab and saliva samples collected using the easily accessible Swan-brand cigarette filter, providing a complete workflow for COVID-19 diagnostics in low-resource settings.
Sialylation of vasorin by ST3Gal1 facilitates TGF‐β1‐mediated tumor angiogenesis and progression (2018)

ST3Gal1 is a key sialyltransferase which adds α2,3‐linked sialic acid to substrates and generates core 1 O ‐glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1 ‐silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF‐β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC‐MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O ‐glycans are sialyl‐3T and disialyl‐T. ST3GAL1 ‐silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF‐β1 by 2‐ to 3‐fold and thereby dampening TGF‐β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse‐free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence ( p = 0.025, HR = 2.967, 95% CI = 1.14–7.67). Since TGF‐β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF ‐ β1 upregulates ST3Gal1 to circumvent the negative impact of VASN.
105 Impact of Antimicrobial Dipping Solutions on Post-Operative Infection Rates in Diabetic Patients Undergoing Primary Insertion of a Coloplast Titan Inflatable Penile Prosthesis (2020)

Penile prostheses (PP) that are dipped in antimicrobial solutions can be specially selected by the implanter and tailored towards the patient. The best choice for antimicrobial solution is widely debated and remains a surgeon’s preference. We conducted a multi-institutional study of diabetic patients undergoing primary Coloplast Titan PP implantation and compared post-operative outcomes based on the antimicrobial solutions used for dipping. Between April 2003 and May 2018, data was collected from 18 different institutions, and charts of 473 patients with diabetes receiving primary PP implantation with Coloplast Titan devices were reviewed. Antibiotics and antifungals used for device impregnation were recorded for each patient. Primary outcome was post-operative infection rate and secondary outcomes were explantation and revision rates. Patients had a median follow-up time of 7 months (range: 0 – 157). Patients were included in the analysis only if they had complete information regarding peri-procedural antimicrobial dip use and the above mentioned outcomes. Univariate comparisons of proportions were completed for rates of infection, explantation, and revision between different antimicrobial regimens.
Scalable inference in max-margin topic models (2013)

Topic models have played a pivotal role in analyzing large collections of complex data. Besides discovering latent semantics, supervised topic models (STMs) can make predictions on unseen test data. By marrying with advanced learning techniques, the predictive strengths of STMs have been dramatically enhanced, such as max-margin supervised topic models, state-of-the-art methods that integrate max-margin learning with topic models. Though powerful, max-margin STMs have a hard non-smooth learning problem. Existing algorithms rely on solving multiple latent SVM subproblems in an EM-type procedure, which can be too slow to be applicable to large-scale categorization tasks.
Strong .pi.-antibonding effects on the electronic structures of complexes with charge-delocalized macrocyclic ligands (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStrong .pi.-antibonding effects on the electronic structures of complexes with charge-delocalized macrocyclic ligandsHisashi Okawa and Daryle H. BuschCite this: Inorg. Chem. 1979, 18, 6, 1555–1558Publication Date (Print):June 1, 1979Publication History Published online1 May 2002Published inissue 1 June 1979https://pubs.acs.org/doi/10.1021/ic50196a033https://doi.org/10.1021/ic50196a033research-articleACS PublicationsRequest reuse permissionsArticle Views87Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Is the Grass Greener on the Other Side? What Went Wrong with French Regions, and the Implications for England (1997)

The experience of France’s elected regions offers both comfort and admonition to English reformers. That the centralised, unitary French state can establish regions as popularly legitimate and fully functioning governing institutions in a short space of time is an optimistic sign. Yet, notwithstanding Europeanisation and some examples of innovation, regions have been constrained by poor performance, weak leadership, the burgeoning departmental system of administration and the newly consolidated power of the regional state. The main lessons for England are: the need to establish effective powers at the outset; the inappropriateness of halfway houses to direct elections; the difficulties of using existing administrative boundaries; and the dangers of competition between tiers of government for an economic development role.
Forced Intercalation (FIT)-Aptamers (2019)

Aptamers are oligonucleotide sequences that can be evolved to bind to various analytes of interest. Here, we present a general design strategy that transduces an aptamer-target binding event into a fluorescence readout via the use of a viscosity-sensitive dye. Target binding to the aptamer leads to forced intercalation (FIT) of the dye between oligonucleotide base pairs, increasing its fluorescence by up to 20-fold. Specifically, we demonstrate that FIT-aptamers can report target presence through intramolecular conformational changes, sandwich assays, and target-templated reassociation of split-aptamers, showing that the most common aptamer-target binding modes can be coupled to a FIT-based readout. This strategy also can be used to detect the formation of a metallo-base pair within a duplexed strand and is therefore attractive for screening for metal-mediated base pairing events. Importantly, FIT-aptamers reduce false-positive signals typically associated with fluorophore-quencher based systems, quantitatively outperform FRET-based probes by providing up to 15-fold higher signal to background ratios, and allow rapid and highly sensitive target detection (nanomolar range) in complex media such as human serum. Taken together, FIT-aptamers are a new class of signaling aptamers which contain a single modification, yet can be used to detect a broad range of targets.
Abstract 10077: Intra-Arterial Administration of Bone Marrow Mononuclear Cells in Patients with Critical Limb Ischemia -- a Randomized-Start, Placebo-Controlled Trial (PROVASA) (2010)

Background: Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are...
Data sharing in group work (1987)

Data sharing is fundamental to computer-supported cooperative work: People share information through explicit communication channels and through their coordinated use of shared databases. This paper examines the data management requirements of group work applications on the basis of experience with three prototype systems and on observations from the literature. Database and object management technologies that support these requirements are briefly surveyed, and unresolved issues in the particular areas of access control and concurrency control are identified for future research.
Noise Reduction Effect of Folding-integration ADC in an 8K Image Sensor driven at Various Frame Rates (2020)

This paper describes the noise reduction effect of a folding-integration (FI) ADC applied to an 8K image sensor. To maximize the sampling number in correlated multiple sampling (CMS), we implement duplicated pixel source followers, which are operated alternately to reduce the time needed for them to settle. This architecture facilitates sampling numbers of 6, 14, and 30 at 120, 60, and 30 fps, respectively. To investigate the relationship between noise reduction effect and sampling number, the input referred noise of the readout circuit from the pixel-to-column ADC is estimated via theoretical calculations and compared with measurements. As a result, the random noise levels of 3.2, 2.0, and 1.5 e <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-</sup> were measured at sampling numbers of 6, 14, and 30, respectively, corresponding well with the calculated results. Furthermore, theoretical calculations revealed that the thermal noise component is dominant at higher frame rates while 1/f noise from the source follower becomes dominant at lower frame rates.
Involvement of Iron (Ferric) Reduction in the Iron Absorption Mechanism of a Trivalent Iron-Protein Complex (Iron Protein Succinylate (2000)

Iron protein succinylate is a non-toxic therapeutic iron compound. We set out to characterise the structure of this compound and investigate the importance of digestion and intestinal reduction in determining absorption of the compound. The structure of the compound was investigated by variable temperature Mössbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioactive compound force fed to mice. Reduction of the compound was determined by in vitro incubation with intestinal fragments. The compound was found to contain only ferric iron, present as small particles including sizes below 10 nm. The iron was released rapidly to chelators. Digestion with trypsin reduced the molecular size of the compound. Intestinal absorption of the compound was inhibited by a ferrous chelator (ferrozine), indicating that reduction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pepsin, followed by pancreatin, released soluble iron complexes with an increased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric species which may be reduced at the mucosal surface to provide ferrous iron for membrane transport into enterocytes.
Efficiently prefetching complex address patterns (2015)

Prior work in hardware prefetching has focused mostly on either predicting regular streams with uniform strides, or predicting irregular access patterns at the cost of large hardware structures. This paper introduces the Variable Length Delta Prefetcher (VLDP), which builds up delta histories between successive cache line misses within physical pages, and then uses these histories to predict the order of cache line misses in new pages. One of VLDP's distinguishing features is its use of multiple prediction tables, each of which stores predictions based on a different length of input history. For example, the first prediction table takes as input only the single most recent delta between cache misses within a page, and attempts to predict the next cache miss in that page. The second prediction table takes as input a sequence of the two most recent deltas between cache misses within a page, and also attempts to predict the next cache miss in that page, and so on with additional tables. Longer histories generally yield more accurate predictions, so VLDP prefers to make predictions based on the longest history table that has a matching entry.
08241 Summary – Transactional Memory : From Implementation to Application (2008)

A goal of current multiprocessor software design is to introduce parallelism into software applications by allowing operations that do not conflict in accessing memory to proceed concurrently. The key tool in designing concurrent data structures has been the use of locks. Unfortunately, course grained locking is easy to program with, but provides very poor performance because of limited parallelism. Fine-grained lock-based concurrent data structures perform exceptionally well, but designing them has long been recognized as a difficult task better left to experts. If concurrent programming is to become ubiquitous, researchers agree that one must develop alternative approaches that simplify code design and verification.
Synthesis, platelet aggregation inhibitory activity, and in vivo antithrombotic activity of new 1,4-dihydropyridines (1988)

A series of 1,4-dihydropyridines (DHP) bound to 1,2-benzisothiazol-3-ones were synthesized and evaluated for their ability to inhibit platelet aggregation induced by collagen in human platelet-rich plasma (PRP) and to protect mice against experimental thrombosis. The results showed that the compounds were in vitro inhibitors of collagen-induced platelet aggregation. Most of them were also effective in reducing mortality in the mouse antithrombotic assay. 2-(1,1,3-Trioxo-2,3-dihydro-1,2-benzisothiazol-2-yl)ethyl 2,6-dimethyl-5-(ethoxycarbonyl)-4-methyl-1,4-dihydropyridinecarboxyla te (4A) is the most promising compound. This compound did not show any cardiovascular effects either in the anesthetized cat or in the anesthetized rat at iv doses up to 750 or 500 micrograms/kg, respectively. Likewise, antiplatelet and cardiovascular effects of compound 4A were simultaneously studied in anesthetized rats and compared with those of nitrendipine.
A More Efficient AES Threshold Implementation (2013)

Abstract. Threshold Implementations provide provable security against first-order power analysis attacks for hardware and software implementations. Like masking, the approach relies on secret sharing but it differs in the implementation of logic functions. At Eurocrypt 2011 Moradi et al. published the to date most compact Threshold Implementation of AES-128 encryption. Their work shows that the number of required random bits may be an additional evaluation criterion, next to area and speed. We present a new Threshold Implementation of AES-128 encryption that is 18 % smaller, 7.5 % faster and that requires 8 % less random bits than the implementation from Eurocrypt 2011. In addition, we provide results of a practical security evaluation based on real power traces in adversary-friendly conditions. They confirm the first-order attack resistance of our implementation and show good resistance against higher-order attacks.
Modeling ex vivo tumor-infiltrating lymphocyte expansion from established solid malignancies (2021)

Abstract Adoptive transfer of tumor-infiltrating lymphocytes (TIL) elicits the regression of metastatic malignancies, yet a low proportion of patients achieve complete durable responses. The high incidence of relapse in these patients highlights the need to better understand mechanisms of tumor escape from T cell control. While melanoma has provided the foundation for developing TIL therapy, much less is known about TIL efficacy and relapse in other malignancies. We sought to investigate TIL characteristics in mouse tumors which have not been studied in this setting. Here, we expanded murine TIL ex vivo in IL-2 from fragments of multiple tumor models, including oral cavity cancer models of varying immunogenicity. Additionally, TIL was expanded from pmel-1 mice bearing B16 melanoma, yielding an enriched population of tumor-infiltrating TCR transgenic T cells. Murine TILs are similar to human TIL in that they express high levels of inhibitory receptors (PD-1, Tim-3, etc.) and can be expanded ex vivo in IL-2 extensively. Of clinical relevance, we draw parallels between murine and patient TIL, evaluating relationships between PD-1, Lag-3, and Tim-3 on TILs from a cohort of oral cavity cancer patients. This platform can be used by labs even in the absence of clinical specimens or clean cell facilities and will be important to more broadly understand TIL phenotypes across many different malignancies.
Structure From Motion With Directional Correspondence for Visual Odometry (2011)

This report presents two efficient solutions to the two-view, relative pose problem from three image point correspondences and one common reference direction. This three-plus-one problem can be used either as a substitute for the classic five-point algorithm using a vanishing point for the reference direction, or to make use of an inertial measurement unit commonly available on robots and mobile devices, where the gravity vector becomes the reference direction. We provide a simple closed-form solution and a solution based on techniques from algebraic geometry and investigate numerical and computational advantages of each approach. In a set of real experiments, we demonstrate the power of our approach by comparing it to the five-point method in a hypothesize-and-test visual odometry setting.
Persistent infection of macaques with simian-human immunodeficiency viruses (1995)

Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis.