gebhart/patrepeval huggingface dataset:
Immunoproteomics (2004)

The mammalian immune system has evolved to display fragments of protein antigens derived from microbial pathogens to immune effector cells. These fragments are typically peptides liberated from the intact antigens through distinct proteolytic mechanisms that are subsequently transported to the cell surface bound to chaperone-like receptors known as major histocompatibility complex (MHC) molecules. These complexes are then scrutinized by effector T cells that express clonally distributed T cell receptors with specificity for specific MHC-peptide complexes. In normal uninfected cells, this process of antigen processing and presentation occurs continuously, with the resultant array of self-antigen-derived peptides displayed on the surface of these cells. Changes in this peptide landscape of cells act to alert immune effector cells to changes in the intracellular environment that may be associated with infection, malignant transformation, or other abnormal cellular processes, resulting in a cascade of events that result in their elimination. Because peptides play such a crucial role in informing the immune system of infection with viral or microbial pathogens and the transformation of cells in malignancy, the tools of proteomics, in particular mass spectrometry, are ideally suited to study these immune responses at a molecular level. Here we review recent advances in the studies of immune responses that have utilized mass spectrometry and associated technologies, with specific examples from collaboration between our laboratories.
Acyl coenzyme A : cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis (2001)

Two enzymes are responsible for cholesterol ester formation in tissues, acyl coenzyme A : cholesterol acyltransferase types 1 and 2 (ACAT1 and ACAT2). The available evidence suggests different cell locations, membrane orientations, and metabolic functions for each enzyme. ACAT1 and ACAT2 gene disruption experiments in mice have shown complementary results, with ACAT1 being responsible for cholesterol homeostasis in the brain, skin, adrenal, and macrophages. ACAT1 −/− mice have less atherosclerosis than their ACAT1 +/+ counterparts, presumably because of the decreased ACAT activity in the macrophages. By contrast, ACAT2 −/− mice have limited cholesterol absorption in the intestine, and decreased cholesterol ester content in the liver and plasma lipoproteins. Almost no cholesterol esterification was found when liver and intestinal microsomes from ACAT2 −/− mice were assayed. Studies in non-human primates have shown the presence of ACAT1 primarily in the Kupffer cells of the liver, in non-mucosal cell types in the intestine, and in kidney and adrenal cortical cells, whereas ACAT2 is present only in hepatocytes and in intestinal mucosal cells. The membrane topology for ACAT1 and ACAT2 is also apparently different, with ACAT1 having a serine essential for activity on the cytoplasmic side of the endoplasmic reticulum membrane, whereas the analogous serine is present on the lumenal side of the endoplasmic reticulum for ACAT2. Taken together, the data suggest that cholesterol ester formation by ACAT1 supports separate functions compared with cholesterol esterification by ACAT2. The latter enzyme appears to be responsible for cholesterol ester formation and secretion in lipoproteins, whereas ACAT1 appears to function to maintain appropriate cholesterol availability in cell membranes.
Monthly cholecalciferol administration in haemodialysis patients: a simple and efficient strategy for vitamin D supplementation (2009)

Long-term monthly administration of oral cholecalciferol (100 000 IU) was a safe, effective, inexpensive and simple method for correcting vitamin D deficiency in almost 90% of the HD patients in this study and led to optimal compliance. The most evident consequences were a slight decrease in the levels of PTH and bone markers and an increase in the level of serum 1,25(OH)(2)D.
A Wireless Passive Sensor for Temperature Compensated Remote pH Monitoring (2013)

Temperature must be accounted for in order to provide accurate measurements in electrode-based pH sensors. We present an integrated wireless passive sensor for remote pH monitoring employing temperature compensation. The sensor is a resonant circuit consisting of a planar spiral inductor connected in parallel to a temperature-dependent resistor (thermistor) and a voltage-dependent capacitor (varactor). A pH combination electrode consisting of an iridium/iridium oxide sensing electrode and a silver/silver chloride reference electrode, is connected in parallel with the varactor. A potential difference change across the electrodes due to pH variation of the solution changes the voltage-dependent capacitance and shifts the resonant frequency, while temperature of the solution affects the resistance and changes the quality factor of the sensor. An interrogator coil is inductively coupled to the sensor inductor and remotely tracks the resonant frequency and quality factor of the sensor. The sensor is calibrated for temperature over a range of 25°C -55°C and pH over a 1.5-12 dynamic range. By employing temperature compensation, a measurement accuracy of less than 0.1 pH is achieved and the response time of the sensor is demonstrated to be less than 1 s. The sensor overcomes the pH measurement error due to the temperature dependence of electrode-based passive pH sensors and has applications in remote pH monitoring where temperature varies over a wide range.
Oligosaccharide Sequences Attached to an Inert Support (SYNSORB) as Potential Therapy for Antibiotic-Associated Diarrhea and Pseudomembranous Colitis (1994)

Toxin A produced by Clostridium difficile, the causative agent of pseudomembranous colitis and antibiotic-associated diarrhea, was shown to bind to synthetic oligosaccharide sequences attached to an inert support (SYNSORB). The oligosaccharide sequences that bind to toxin A were related to sequences previously identified as potential receptors for the toxin. Various SYNSORBs containing a variety of oligosaccharides were examined for their potential to neutralize toxin A activity from toxin-containing solutions as well as clinical stool samples from patients with either pseudomembranous colitis or antibiotic-associated diarrhea. The results from neutralization experiments suggest SYNSORB can effectively neutralize toxin A activity from stool samples and thus could serve as a potential therapy for C. difficile-associated diarrhea.
RNA Sequencing of Formalin-Fixed, Paraffin-Embedded Specimens for Gene Expression Quantification and Data Mining (2016)

<i>Background</i>. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (<i>N</i> = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. <i>Results</i>. Both rRNA depletion methods produced consistent data between the technical replicates. We found that the RNase H method produced higher quality RNAseq data as compared to the Ribo-Zero method. In addition, we evaluated the RNAseq data generated from the FFPE tissue samples for noncoding RNA, including lncRNA, enhancer/super enhancer RNA, and single nucleotide variation (SNV). We found that the RNase H is more suitable for detecting high-quality, noncoding RNAs as compared to the Ribo-Zero and provided more consistent molecular subtype identification between replicates. Unfortunately, neither method produced reliable SNV data. <i>Conclusions</i>. In conclusion, for FFPE specimens, the RNase H rRNA depletion method performed better than the Ribo-Zero. Neither method generates data sufficient for SNV detection.
Static load classification for improving the value predictability of data-cache misses (2002)

While caches are effective at avoiding most main-memory accesses, the few remaining memory references are still expensive. Even one cache miss per one hundred accesses can double a program's execution time. To better tolerate the data-cache miss latency, architects have proposed various speculation mechanisms, including load-value prediction. A load-value predictor guesses the result of a load so that the dependent instructions can immediately proceed without having to wait for the memory access to complete. To use the prediction resources most effectively, speculation should be restricted to loads that are likely to miss in the cache and that are likely to be predicted correctly. Prior work has considered hardware- and profile-based methods to make these decisions. Our work focuses on making these decisions at compile time. We show that a simple compiler classification is effective at separating the loads that should be speculated from the loads that should not. We present results for a number of C and Java programs and demonstrate that our results are consistent across programming languages and across program inputs.
Synthetic biology, tinkering biology, and artificial biology. What are we learning? (2010)

While chemical theory cannot yet support an engineering vision that allows molecules, DNA sequences, and proteins to be interchangeable parts in artificial constructs without "tinkering", progress can be made in synthetic biology by pursuing challenges at the limits of existing theory. These force scientists across uncharted terrain where they must address unscripted problems where, if theory is inadequate, failure results. Thus, synthesis drives discovery and paradigm change in ways that analysis cannot. Further, if failures are analyzed, new theories emerge. Here, we illustrate this by synthesizing an artificial genetic system capable of Darwinian evolution, a feature theorized to be universal to life.
ATM (ataxia telangiectasia mutated): expanding roles in the DNA damage response and cellular homeostasis (2001)

DNA damage is one of the most acute threats to cellular homeostasis and life. The cell responds to such damage by activating a vast array of responses, ranging from DNA repair to numerous signalling pathways, which temporarily slow down the cellular life cycle while the damage is being repaired. Sophisticated relays convey the DNA damage alarm to all these systems immediately after damage infliction. Such relays must be capable of sensing the damage and rapidly creating functional contact with many signalling networks. The ataxia telangiectasia mutated (ATM) protein is a prominent example of such a relay. It responds swiftly to a critical DNA damage - the double strand break (DSB) - by phosphorylating key proteins in numerous signalling pathways. Evidence is emerging, however, that the ATM protein might also be involved in other processes related to cellular homeostasis, which are not directly associated with the damage response. ATM is the protein product of the gene mutated in the multisystem disorder ataxia-telangiectasia (AT), which is characterized by neuronal degeneration, immunodeficiency, chromosomal instability and cancer predisposition. The AT phenotype and the functions of the ATM protein revealed to date demonstrate the exceptionally multifaceted nature of this protein.
MCF7 Side Population Cells with Characteristics of Cancer Stem/Progenitor Cells Express the Tumor Antigen MUC1 (2008)

Chemotherapy, radiation, and growth inhibitory drugs preferentially eliminate actively growing cancer cells. Cancer recurrence is currently thought to be due to nondividing cancer stem/progenitor cells that are resistant to these therapies. Different therapeutic approaches need to be considered for the elimination of the cancer stem cell population. Immunotherapy is one such approach. In addition to specificity and lack of toxicity, immunotherapy targets cancer cells irrespective of their state of proliferation, as long as they express particular tumor antigens. For that reason, it is important to examine if the tumor antigens that are currently being tested as immunotherapeutic agents are also present on cancer stem cells. This study aimed to determine if one well-known tumor antigen, MUC1, which is being tested as an immunotherapy target on tumor cells, is also expressed on the quiescent cancer stem/progenitor cells. We used the so-called side population (SP) cells found in the MCF7 breast cancer cell line, which we first confirmed by cell surface markers and gene profiling to be highly enriched in cells that fulfill specific functional, phenotypic, and molecular criteria for being tumor stem/progenitor cells. We show that these cells express MUC1 and give rise to MUC1(+) tumors in vivo, which maintain the MUC1(+) SP population. MUC1 on SP cells is hypoglycosylated and heavily sialylated; the characteristics of the tumor-specific form were expressed on mature cancer cells and recognized by tumor-specific T cells and antibodies. This suggests that stem/progenitor cells, like mature tumor cells, would be targets of MUC1-directed immunotherapy.
Thermogelling properties of purified poloxamer 407 (2017)

Poloxamers are triblock copolymers with a center block of hydrophobic polypropylene oxide (PPO) flanked by two hydrophilic polyethyleneoxide (PEO) blocks. Among this family of copolymers, poloxamer 407 is a non-ionic surfactant with reversible gelation properties above a particular polymer concentration and a particular temperature. Easy preparation of poloxamer 407 based sterile injectable formulations have made this copolymer a good candidate for drug delivery, specifically when controlled release of the drug is required. Previously, the applications of compendial poloxamer 407 preparations were demonstrated; however, low viscosity, poor elasticity, and sol-to-gel transition temperature (T<sub>sol-gel</sub>) over a wide temperature range were observed. A purification process was introduced to eliminate impurities and low molecular weight copolymer molecules from the compendial poloxamer 407 resulting in higher viscosity values with T<sub>sol-gel</sub> in a narrow temperature range. Here, poloxamer 407 was purified based on the proposed process and the rheological and analytical evaluation of the purified poloxamer 407 was conducted and compared to unpurified, compendial poloxamer 407. Then, the impact of poloxamer 407 concentration on gel formation was evaluated. For drug delivery applications, the effect of relevant buffer salts and the effect of addition of ethanol to the poloxamer 407 solutions were rheologically evaluated.
Fast direct solution of standard moment-method matrices (1998)

All of the matrices which arise in the method-of-moments solution of scattering and antenna problems have a hidden structure. This structure is due to the physics of electromagnetic interactions. Matrix-algebra routines are used to uncover this structure in moment-method matrices, after they have been calculated. This structure is used to create a sparse representation of the matrix. Although this step involves an approximation, the error involved can be nearly as small as the precision of the calculation. Then, without further approximation, a sparse representation of the LU factorization of this matrix is computed. A significant speed improvement is realized over that of the standard LU factorization of this matrix. The resulting method can be added to any of a variety of moment-method programs to solve the matrix problem more quickly, and with less computer memory. For large problems this is the time-critical operation, so this allows larger problems to be solved. The computer program we have written can be used immediately with most moment-method programs, since it amounts to simply a better matrix-inversion package. The method presented is referred to as the LU sparse integral factored representation (LUSIFER).
Retinoic acid enhances neuronal proliferation and astroglial differentiation in cultures of CNS stem cell-derived precursors (1998)

Stem cells isolated from the embryonic day 14 mouse striatum proliferate in response to epidermal growth factor (EGF). These stem cells produce clonally derived clusters of undifferentiated cells (spheres) which, in turn, produce neurons, astrocytes, and oligodendrocytes. Reverse transcription followed by polymerase chain reaction showed that EGF-generated spheres express several of the retinoid receptors. Thus, we asked whether all-trans retinoic acid (ATRA) could regulate the differentiation or proliferation of central nervous system stem cell-derived progeny. Under conditions that promote differentiation, cultures of dissociated spheres showed a dose-dependent increase in neuron numbers in response to ATRA. At the most effective neurogenic concentration (0.1 microM ATRA), neuron production increased two- to threefold. However, no difference in the total numbers of control and treated cells was observed. Delayed addition experiments suggest that responsive cells must be exposed to ATRA within the first 24 h in culture. Bromodeoxyuridine incorporation labeling indicates that the ATRA-generated neurons are derived from a mitotically active population of cells. Under conditions that promote glial progenitor cell division, however, ATRA attenuated proliferation (maximum of 60% decrease with 0.1 microM ATRA), accompanied by an increase in the number of glial fibrillary acidic protein-immunoreactive astrocytes. These results suggest that retinoids can regulate the proliferation of mitotically active EGF-responsive stem cell progeny to enhance neurogenesis and astrocyte differentiation.
Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. (1992)

A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.
Poxviral Protein A46 Antagonizes Toll-like Receptor 4 Signaling by Targeting BB Loop Motifs in Toll-IL-1 Receptor Adaptor Proteins to Disrupt Receptor:Adaptor Interactions (2012)

Toll-like receptors (TLRs) have an anti-viral role in that they detect viruses, leading to cytokine and IFN induction, and as such are targeted by viruses for immune evasion. TLR4, although best known for its role in recognizing bacterial LPS, is also strongly implicated in the immune response to viruses. We previously showed that the poxviral protein A46 inhibits TLR4 signaling and interacts with Toll-IL-1 receptor (TIR) domain-containing proteins of the receptor complex. However the exact molecular mechanism whereby A46 disrupts TLR4 signaling remains to be established, and may yield insight into how the TLR4 complex functions, since viruses often optimally target key residues and motifs on host proteins for maximal efficiency. Here we show that A46 targets the BB loop motif of TIR proteins and thereby disrupts receptor:adaptor (TLR4:Mal and TLR4:TRAM), but not receptor:receptor (TLR4:TLR4) nor adaptor:adaptor (Mal:MyD88, TRAM:TRIF, and Mal:Mal) TIR interactions. The requirement for an intact BB loop for TIR adaptor interactions correlated with the protein:protein interfaces antagonized by A46. We previously discovered a peptide fragment derived from A46 termed VIPER (Viral Inhibitory Peptide of TLR4), which specifically inhibits TLR4 responses. Here we demonstrate that the region of A46 from which VIPER is derived represents the TLR4-specific inhibitory motif of the intact protein, and is essential for A46:TRAM interactions. This study provides the molecular basis for pathogen subversion of TLR4 signaling and clarifies the importance of TIR motif BB loops, which have been selected for viral antagonism, in the formation of the TLR4 complex.
A non-intrusive isolation approach for soft cores (2007)

Cost effective SOC test strongly hinges on parallel, independent test of SOC cores, which can only be ensured through proper core isolation techniques. While a core isolation mechanism can provide controllability and observability at the core I/O interface, its implementation may have various implications on area, functional timing, test time and data volume, and at-speed coverage on the core interface. This paper proposed a non-intrusive core isolation technique that is based on the utilization of existing core registers for isolating the core. The authors provide a core register partitioning algorithm that is capable of identifying the core interface registers, and of robustly isolating a core, resulting in a computationally efficient core isolation implementation that is area and performance efficient at the same time. The proposed isolation technique also ensures minimal test time increase and no at-speed coverage loss on the core interface, offering an elegant solution for soft cores, and thus enabling significant SOC test cost reductions
Cofactor Regeneration of both NAD+ from NADH and NADP+ from NADPH:NADH Oxidase from Lactobacillus sanfranciscensis (2003)

Abstract A possible solution for the regeneration of NAD + from NADH is the oxidation of NADH with concomitant reduction of oxygen catalyzed by NADH oxidase (E. C. 1.6.‐.‐). We employ NADH oxidase from Lactobacillus sanfranciscensis , which reduces O 2 to innocuous H 2 O, and ( R )‐alcohol dehydrogenase [( R )‐ADH] from Lactobacillus brevis to perform enantioselective oxidation of racemic phenylethanol to acetophenone and ( S )‐phenylethanol with regeneration of either NADH or NADPH to their respective oxidized precursors. NADH oxidase from L. sanfranciscensis accepts both NADH and NADPH; in contrast, the wild‐type ( R )‐ADH only accepts NADP(+)(H) whereas its G37D mutant strongly prefers NAD(+)(H). Highly purified. NADH oxidase (221 U/mg, two‐step protocol) was coupled with wild‐type ADH from L. brevis on NADP(H) and mutant ADH from L. brevis on NAD(H) to achieve 50% conversion of racemic phenylethanol to ( S )‐phenylethanol and acetophenone. Depending on the relative concentration of alcohol to cofactor, up to more than 100 turnovers were observed. We believe that this is the first demonstration of a regeneration scheme for both NAD + from NADH and NADP + from NADPH with the same enzyme.