gebhart/patrepeval huggingface dataset:
Sorbitol Dehydrogenase Overexpression and Other Aspects of Dysregulated Protein Expression in Human Precancerous Colorectal Neoplasms: A Quantitative Proteomics Study (2014)

Colorectal adenomas are cancer precursor lesions of the large bowel. A multitude of genomic and epigenomic changes have been documented in these preinvasive lesions, but their impact on the protein effectors of biological function has not been comprehensively explored. Using shotgun quantitative MS, we exhaustively investigated the proteome of 30 colorectal adenomas and paired samples of normal mucosa. Total protein extracts were prepared from these tissues (prospectively collected during colonoscopy) and from normal (HCEC) and cancerous (SW480, SW620, Caco2, HT29, CX1) colon epithelial cell lines. Peptides were labeled with isobaric tags (iTRAQ 8-plex), separated via OFFGEL electrophoresis, and analyzed by means of LC-MS/MS. Nonredundant protein families (4325 in tissues, 2017 in cell lines) were identified and quantified. Principal component analysis of the results clearly distinguished adenomas from normal mucosal samples and cancer cell lines from HCEC cells. Two hundred and twelve proteins displayed significant adenoma-related expression changes (q-value < 0.02, mean fold change versus normal mucosa ±1.4), which correlated (r = 0.74) with similar changes previously identified by our group at the transcriptome level. Fifty-one (∼25%) proteins displayed directionally similar expression changes in colorectal cancer cells (versus HCEC cells) and were therefore attributed to the epithelial component of adenomas. Although benign, adenomas already exhibited cancer-associated proteomic changes: 69 (91%) of the 76 protein up-regulations identified in these lesions have already been reported in cancers. One of the most striking changes involved sorbitol dehydrogenase, a key enzyme in the polyol pathway. Validation studies revealed dramatically increased sorbitol dehydrogenase concentrations and activity in adenomas and cancer cell lines, along with important changes in the expression of other enzymes in the same (AKR1B1) and related (KHK) pathways. Dysregulated polyol metabolism might represent a novel facet of metabolome remodeling associated with tumorigenesis.
Patterns of User Experience in Performance Programming (2015)

This paper presents a pattern language for user experiences in live coding. It uses a recently defined analytic framework that has developed out of the Cognitive Dimensions of Notations and related approaches. The focus on performance programming offers particular value in its potential to construct rigorous accounts of the experiences of both performers (the live coder) and audiences. Although developed as an account of live coding, the findings promise to be relevant to a wider range of performance programming contexts, which could benefit from analysis in terms of live coding, if a systematic framework of this kind were available.<br> The paper provides a detailed analytic commentary, drawing on the broadly diverse body of prior live coding practice, but using music live coding as a central running example. The findings demonstrate the advantage of rigorous analysis from an independent theoretical perspective, and suggest the potential for future work that might draw on this pattern language as a basis for empirical investigations of user experience, and as a theoretical grounding in practice-led design of new live coding languages and tools.
Hydrogen embrittlement of cold-worked metastable austenitic stainless steels. (1991)

The effect of cold-working on hydrogen embrittlement of metastable austenitic stainless steels has been investigated. The specimens were made of SUS302 and SUS304, which had different austenite stabilities, and were cold-worked by 20% to 80%. Hydrogen embrittlement of H-charged specimens was measured by bend testing. The main results are as follows:
Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment (2022)

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.
Nicotinamide mononucleotide adenylyl transferase 1 protects against acute neurodegeneration in developing CNS by inhibiting excitotoxic-necrotic cell death (2011)

Hypoxic-ischemic (H-I) injury to the developing brain is a significant cause of morbidity and mortality in humans. Other than hypothermia, there is no effective treatment to prevent or lessen the consequences of neonatal H-I. Increased expression of the NAD synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) has been shown to be neuroprotective against axonal injury in the peripheral nervous system. To investigate the neuroprotective role of Nmnat1 against acute neurodegeneration in the developing CNS, we exposed wild-type mice and mice overexpressing Nmnat1 in the cytoplasm (cytNmnat1-Tg mice) to a well-characterized model of neonatal H-I brain injury. As early as 6 h after H-I, cytNmnat1-Tg mice had strikingly less injury detected by MRI. CytNmnat1-Tg mice had markedly less injury in hippocampus, cortex, and striatum than wild-type mice as assessed by loss of tissue volume 7 d days after H-I. The dramatic protection mediated by cytNmnat1 is not mediated through modulating caspase3-dependent cell death in cytNmnat1-Tg brains. CytNmnat1 protected neuronal cell bodies and processes against NMDA-induced excitotoxicity, whereas caspase inhibition or B-cell lymphoma-extra large (Bcl-XL) protein overexpression had no protective effects in cultured cortical neurons. These results suggest that cytNmnat1 protects against neonatal HI-induced CNS injury by inhibiting excitotoxicity-induced, caspase-independent injury to neuronal processes and cell bodies. As such, the Nmnat1 protective pathway could be a useful therapeutic target for acute and chronic neurodegenerative insults mediated by excitotoxicity.
Microfluidics for bacterial chemotaxis (2010)

Microfluidics is revolutionizing the way we study the motile behavior of cells, by enabling observations at high spatial and temporal resolution in carefully controlled microenvironments. An important class of such behavior is bacterial chemotaxis, which plays a fundamental role in a broad range of processes, including disease pathogenesis, biofilm formation, bioremediation, and even carbon cycling in the ocean. In biophysical research, bacterial chemotaxis represents a powerful model system to understand how cells and organisms sense and respond to gradients. Using microfluidics to study chemotaxis of free-swimming bacteria presents experimental challenges that are distinct from those arising in chemotaxis studies of surface-adherent cells. Recently, these challenges have been met by the development of advanced microdevices, able to generate flow-free, steady gradients of arbitrary shape. Much attention to date has been focused on tool development. Yet, we are now at an exciting turning point where science begins to balance technology. Indeed, recent microfluidic studies provided new insights on both the mechanisms governing bacterial gradient sensing (e.g. tuning of response sensitivity, discrimination between conflicting gradients) and the large-scale consequences of chemotaxis (e.g. in the oceans). Here we outline the principles underlying recently proposed gradient generators for bacterial chemotaxis, illustrate the advantage of the microfluidic approach through selected examples, and identify a broader set of scientific questions that may now be addressed with this rapidly developing technology. The latest generation of microfluidic gradient generators, in particular, holds appeal for both biophysicists seeking to unravel the fundamental mechanisms of bacterial chemotaxis, and ecologists wishing to model chemotaxis in realistic environments. Time is ripe for a deeper integration between technology and biology in fully bringing to bear microfluidics on studies of this fascinating microbial behavior.
ChemInform Abstract: Lewis Acid and/or Lewis Base Catalyzed [3 + 2] Cycloaddition Reaction: Synthesis of Pyrazoles and Pyrazolines. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients (2009)

The objective of this case-control study was to compare the efficacy and toxicity of lenalidomide plus dexamethasone (len/dex) versus thalidomide plus dexamethasone (thal/dex) as initial therapy for newly diagnosed myeloma. We retrospectively studied 411 newly diagnosed patients treated with len/dex (228) or thal/dex (183) at the Mayo Clinic. The differences were similar in a matched-pair analysis that adjusted for age, sex, transplantation status, and dexamethasone dose. The proportions of patients achieving at least a partial response to len/dex and thal/dex were 80.3% versus 61.2%, respectively (P < .001); very good partial response rates were 34.2% and 12.0%, respectively (P < .001). Patients receiving len/dex had longer time to progression (median, 27.4 vs 17.2 months; P = .019), progression-free survival (median, 26.7 vs 17.1 months; P = .036), and overall survival (median not reached vs 57.2 months; P = .018). A similar proportion of patients in the 2 groups experienced at least one grade 3 or 4 adverse event (57.5% vs 54.6%, P = .568). Main grade 3 or 4 toxicities of len/dex were hematologic, mainly neutropenia (14.6% vs 0.6%, P < .001); the most common toxicities in thal/dex were venous thromboembolism (15.3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results.
Fault Attacks on Pairing-Based Protocols: Revisited (2014)

Several papers have studied fault attacks on computing a pairing value e(P,Q), where P is a public point and Q is a secret point. In this paper, we observe that these attacks are in fact effective only on a small number of pairing-based protocols, and that too only when the protocols are implemented with specific symmetric pairings. We demonstrate the effectiveness of the fault attacks on a public-key encryption scheme, an identity-based encryption scheme, and an oblivious transfer protocol when implemented with a symmetric pairing derived from a supersingular elliptic curve with embedding degree 2.
Targeting TNFR2 to overcome acquired adaptive resistance to immune checkpoint blockade (2020)

Abstract Overcoming acquired adaptive immune resistance to anti-PD-1 therapy is imperative for enhancing the efficacy of immune checkpoint blockade (ICB) in solid tumors. Regulatory T cells (Tregs) play a prominent role in the suppressive tumor microenvironment (TME) and are major contributors to adaptive immune resistance. Tregs limit CD8+ T cell reinvigoration and are a promising target for combination therapy. While the clinical efficacy of anti-CTLA4 may be partially explained by restriction of Tregs, its co-administration with anti-PD1 causes significant toxicity. Thus, safer approaches to limit Treg activity are needed. To elucidate the dynamic changes in immuno-regulatory circuits within the TME during ICB, we performed deep immune profiling of peripheral blood and tumors from patients with advanced melanoma prior to (n=7) and after 1 cycle of anti-PD-1 therapy with pembrolizumab (n=9). Tregs were abundant in the TME and retained their immunosuppressive phenotype and functionality following anti-PD-1. Epigenetic, transcriptomic, and proteomic analysis of Tregs after ICB identified tumor necrosis factor receptor 2 (TNFR2) signaling as a possible driver of CD8+ T cell suppression. TNFR2 was preferentially expressed by Tregs in the TME (mean 18.03 %, SD +/− 10.13 %) relative to CD8+ T cells (mean 0.64 %, SD +/− 0.82 %) and peripheral Tregs (mean 3.16 %, SD +/− 3.21 %), suggesting it might be a safe and effective target for combination therapy. Indeed, dual blockade of TNFR2 and PD-1 led to potent CD8+ T cell expansion in two mouse tumor models, and restored sensitivity to ICB in a resistant murine model of melanoma. Our data suggest that anti-TNFR2 might synergize with current ICB by countering the development of adaptive immune resistance.
CMOS high-speed I/Os - present and future (2004)

High-speed I/O circuits, once used only for PHYs, are now widely used for intra-system signaling as well because of their bandwidth, power, area, and cost advantages. This technology enables chips with over 1 Tb/s of I/O bandwidth today and over 10 Tb/s of bandwidth by 2010 as both signaling rates and number of high-speed I/Os increase with process scaling. Key technologies that enable this growth in I/O performance include low-jitter clock circuits and equalized signaling. An analysis of clock jitter and channel interference suggests that signaling rates should track transistor performance to rates of at least 40 Gb/s over boards, back-planes, and short-distance cables.
Development of Stable Nano-Sized Transfersomes as a Rectal Colloid for Enhanced Delivery of Cannabidiol (2022)

Current cannabidiol (CBD) formulations are challenged with unpredictable release and absorption. Rational design of a rectal colloid delivery system can provide a practical alternative<b>.</b> In this study the inherent physiochemical properties of transferosomes were harnessed for the development of a nano-sized transfersomes to yield more stable release, absorption, and bioavailability of CBD as a rectal colloid. Transfersomes composed of soya lecithin, cholesterol, and polysorbate 80 were synthesized via thin film evaporation and characterized for size, entrapment efficiency (%), morphology, CBD release, ex vivo permeation, and physicochemical stability. The optimized formulation for rectal delivery entrapped up to 80.0 ± 0.077% of CBD with a hydrodynamic particle size of 130 nm, a PDI value of 0.285, and zeta potential of -15.97 mV. The morphological investigation via SEM and TEM revealed that the transfersomes were spherical and unilamellar vesicles coinciding with the enhanced ex vivo permeation across the excised rat colorectal membrane. Furthermore, transfersomes improved the stability of the encapsulated CBD for up to 6 months at room temperature and showed significant promise that the transfersomes promoted rectal tissue permeation with superior stability and afforded tunable release kinetics of CBD as a botanical therapeutic with inherent poor bioavailability.
Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction (2021)

The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.
Interaction of Single-Stranded DNA with Curved Carbon Nanotube Is Much Stronger Than with Flat Graphite (2014)

We used single molecule force spectroscopy to measure the force required to remove single-stranded DNA (ssDNA) homopolymers from single-walled carbon nanotubes (SWCNTs) deposited on methyl-terminated self-assembled monolayers (SAMs). The peeling forces obtained from these experiments are bimodal in distribution. The cluster of low forces corresponds to peeling from the SAM surface, while the cluster of high forces corresponds to peeling from the SWCNTs. Using a simple equilibrium model of the single molecule peeling process, we calculated the free energy of binding per nucleotide. We found that the free energy of ssDNA binding to hydrophobic SAMs decreases as poly(A) > poly(G) ≈ poly(T) > poly(C) (16.9 ± 0.1; 9.7 ± 0.1; 9.5 ± 0.1; 8.7 ± 0.1 kBT, per nucleotide). The free energy of ssDNA binding to SWCNT adsorbed on this SAM also decreases in the same order poly(A) > poly(G) > poly(T) > poly(C), but its magnitude is significantly greater than that of DNA-SAM binding energy (38.1 ± 0.2; 33.9 ± 0.1; 23.3 ± 0.1; 17.1 ± 0.1 kBT, per nucleotide). An unexpected finding is that binding strength of ssDNA to the curved SWCNTs is much greater than to flat graphite, which also has a different ranking (poly(T) > poly(A) > poly(G) ≥ poly(C); 11.3 ± 0.8, 9.9 ± 0.5, 8.3 ± 0.2, and 7.5 ± 0.8 kBT, respectively, per nucleotide). Replica-exchange molecular dynamics simulations show that ssDNA binds preferentially to the curved SWCNT surface, leading us to conclude that the differences in ssDNA binding between graphite and nanotubes arise from the spontaneous curvature of ssDNA.
Targeting the Infant Gut Microbiota Through a Perinatal Educational Dietary Intervention: Protocol for a Randomized Controlled Trial (2019)

DERR1-10.2196/14771.
Long-Term safety of Certolizumab Pegol in Crohnʼs Disease: Integrated safety findings on serious adverse events of special interest (2008)

To evaluate safety data collected from studies included in the certolizumab pegol (CZP) Crohn's disease (CD) development program. Serious adverse event (SAE) data of special interest were analyzed from 9 studies including: a 12-week, Phase II, placebo-controlled study (CZP 100, 200, and 400 mg); an 8-week, Phase II, iv single-dose study (CZP 1.25, 5, 10, and 20 mg/kg); 2 pivotal 26-week, placebo-controlled, Phase-III studies1,2 (4-weekly CZP 400 mg sc to Week 26 following CZP or placebo induction [PRECiSE 1] or CZP induction [PRECiSE 2] at Weeks 0, 2, and 4); 2 ongoing, open-label extension studies (CZP 400 mg every 4 weeks in both) for patients completing PRECiSE 1 or 2 (PRECiSE 3) or prematurely terminating either study due to exacerbation of CD (PRECiSE 4); 2 Phase IIIb studies in patients with moderate-to-severe CD who have failed treatment with infliximab (WELCOME: 26 weeks, CZP 400 mg every 2 or 4 weeks; and a Greek study: 14 weeks, CZP 400 mg); and a Phase IIIb, 54-week endoscopy study (MUSIC, CZP 400 mg). A cut-off date for SAE reporting of July 16, 2007 was used in these analyses. The safety population comprised all patients who had received at least 1 dose of study medication. The safety population comprised 2166 patients with a total exposure to CZP of over 2160 patient-years with duration of exposure of up to 3.5 years. Incidence rates (per 100 patient-years) for SAEs of particular interest are shown in Table 1. Seven cases of a solid tumor (excluding non-melanoma skin cancer) were observed: 2 cases each of rectal cancer and small intestinal cancer; and 1 case each of prostate cancer, breast cancer, and metastatic malignant melanoma. Up to the cut-off date of July 16, 2007 there have been no cases of lymphoma in patients receiving CZP in the CD development program. Opportunistic infections (other than tuberculosis) were reported in 3 patients: Herpes zoster, candidiasis, and esophageal candidiasis. No caption available. No caption available. In this integrated analysis of CZP safety in 2166 moderate-to-severe CD patients with over 2160 patient-years exposure, no unexpected safety findings were identified.
Integrative Functional Assays, Chemical Genomics and High Throughput Screening: Harnessing Signal Transduction Pathways to a Common HTS Readout (2006)

Chemical genomics is a drug discovery strategy that relies heavily on high-throughput screening (HTS) and therefore benefits from functional assay platforms that allow HTS against all relevant genomic targets. Receptor Selection and Amplification Technology (R-SAT) is a cell-based, high-throughput functional assay where the receptor stimulus is translated into a measurable cellular response through an extensive signaling cascade occurring over several days. The large biological and chronological separation of stimulus from response provides numerous opportunities for enabling assays and increasing assay sensitivity. Here we review strategies for building homogeneous assay platforms across large gene families by redirecting and/or amplifying signal transduction pathways.
A compact on-chip ECC for low cost flash memories (2002)

A compact on-chip Error Correcting Code/Circuit (ECC) for low cost Flash memories has been developed to minimize the chip size increase. The proposed on-chip ECC implemented on a 64 M NAND Flash memory has suppressed the chip size penalty to 1.9%. Moreover, the cumulative sector error rate can be improved by 4 orders after 10/sup 6/ write/erase cycles.
Data from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death (2023)

&lt;div&gt;Abstract&lt;p&gt;High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061–induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.&lt;/p&gt;&lt;/div&gt;
SARS-CoV-2 and the Missing Link of Intermediate Hosts in Viral Emergence - What We Can Learn From Other Betacoronaviruses (2022)

The emergence of SARS-CoV-2 in 2019 has resulted in a global pandemic with devastating human health and economic consequences. The development of multiple vaccines, antivirals and supportive care modalities have aided in our efforts to gain control of the pandemic. However, the emergence of multiple variants of concern and spillover into numerous nonhuman animal species could protract the pandemic. Further, these events also increase the difficulty in simultaneously monitoring viral evolution across multiple species and predicting future spillback potential into the human population. Here, we provide historic context regarding the roles of reservoir and intermediate hosts in coronavirus circulation and discuss current knowledge of these for SARS-CoV-2. Increased understanding of SARS-CoV-2 zoonoses are fundamental for efforts to control the global health and economic impacts of COVID-19.