gebhart/patrepeval huggingface dataset:
Functional Domain Analysis of the Yeast ABC Transporter Ycf1p by Site-directed Mutagenesis (1999)

The yeast cadmium factor (Ycf1p) is a vacuolar protein involved in resistance to Cd(2+) and to exogenous glutathione S-conjugate precursors in yeast. It belongs to the superfamily of ATP binding cassette transporters, which includes the human cystic fibrosis transmembrane conductance regulator and the multidrug resistance-associated protein. To examine the functional significance of conserved amino acid residues in Ycf1p, we performed an extensive mutational analysis. Twenty-two single amino acid substitutions or deletions were generated by site-directed mutagenesis in the nucleotide binding domains, the proposed regulatory domain, and the fourth cytoplasmic loop. Mutants were analyzed phenotypically by measuring their ability to grow in the presence of Cd(2+). Expression and subcellular localization of the mutant proteins were examined by immunodetection in vacuolar membranes. For functional characterization of the Ycf1p variants, the kinetic parameters of glutathione S-conjugated leukotriene C(4) transport were measured. Our analysis shows that residues Ile(711), Leu(712), Phe(713), Glu(927), and Gly(1413) are essential for Ycf1p expression. Five other amino acids, Gly(663), Gly(756), Asp(777), Gly(1306), and Gly(1311), are critical for Ycf1p function, and two residues, Glu(709) and Asp(821), are unnecessary for Ycf1p biogenesis and function. We also identify several regulatory domain mutants in which Cd(2+) tolerance of the mutant strain and transport activity of the protein are dissociated.
Pinch analysis : a state-of-the-art overview : Techno-economic analysis (1993)

Through much of its fifteen year history Pinch Analysis has been somewhat controversial. Early on, as Pinch Technology, it introduced simple concepts in a field and an era otherwise known for complex mathematical methods. Reports from first industrial applications claimed design improvements so large as to invite incredulity. Moreover, Pinch Analysis was commercialized early in its development when there was little know-how from practical application. This led to several commercial failures and many vested interests. To this day, opinions remain divided. Morgan (M. W. Kellog) reports that Pinch Analysis significantly improves both the process design and the design process. Steinmeyer (Monsanto) is concerned that Pinch Analysis may miss out on ... major opportunity for improvement.... As is often the case when there is a difference of opinion, different parties have different data. Some of the concepts of Pinch Analysis are widely known, others are less well known. Experience with practical application varies. Some organizations have successfully integrated the approach into the design process, others rely on one or two technical experts. In addition, Pinch Analysis has undergone evolution making it difficult for the casual observer to come to an up-to-date assessment. It has evolved from the design of heat exchanger networks into a general methodology for the design of integrated systems ranging from processes to Total Sites. We attempt to give a state-of-the-art overview. It gives a summary of key established concepts with special emphasis on those concepts which are less well known than others. This is followed by a description of eight recent developments. Some of these developments sharpen the focus of the established concepts, others widen the scope. All of them follow the established pattern of Pinch Analysis of setting targets prior to design. The eight developments are: Pressure Drop Optimization; Multiple Base Case Design; Distillation Column Profiles; Low Temperature Process Design; Batch Process Integration; Water and Waste Water Minimization; Total Site Integration; and Emissions Targeting. We concentrate on the essence not the detail. Case studies are described and scope and impact of practical applications are assessed. For details of methodology, the reader is referred to the relevant references. To complete the overview, we provide a comprehensive summary of previous literature. Theory and applications are covered, and a historical perspective is given. The evolution of Pinch is discussed and it is argued that the term Pinch Analysis is more appropriate today that Pinch Technology. Pinch Analysis is used for the scoping and screening of options during targeting prior to design. The choice of utilities, capital cost optimization, changes in the process/reactor/separation system, overall process emissions, etc. are all avaluated prior to design i.e. in analysis mode
Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy? (2007)

Granulocyte colony-stimulating factor (G-CSF), the major cytokine involved in the control of neutrophil production, is used in the clinic for treatment of congenital and acquired neutropenias and to reduce febrile neutropenia before or during courses of intensive cytoreductive therapy. In addition, healthy stem cell donors are treated with G-CSF for mobilization of hematopoietic stem cells in the peripheral blood. Recent studies have uncovered novel roles for G-CSF in myocardial regeneration following cardiac infarction ( 1 – 3 ) and in ameliorating programmed cell death in neuronal cells caused by acute ischemic stroke, thereby reducing the volume of the brain infarct ( 4 ). Thus, it may be anticipated that the therapeutic application of G-CSF will increase considerably in the near future, making careful and timely risk assessment of vital importance. In this issue of the Journal, Hershman et al. ( 5 ) report a two fold increased risk of secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients who received G-CSF (or granulocyte-macrophage CSF) during adjuvant chemotherapy, compared with patients who did not receive growth factor treatment. This and other recent studies raise questions concerning the underlying molecular and cellular mechanisms whereby myeloid growth factors would initiate or accelerate the development of MDS/AML and how to deal with the potential
Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning (1995)

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.
Magic State Distillation: Not as Costly as You Think (2019)

Despite significant overhead reductions since its first proposal, magic state distillation is often considered to be a very costly procedure that dominates the resource cost of fault-tolerant quantum computers. The goal of this work is to demonstrate that this is not true. By writing distillation circuits in a form that separates qubits that are capable of error detection from those that are not, most logical qubits used for distillation can be encoded at a very low code distance. This significantly reduces the space-time cost of distillation, as well as the number of qubits. In extreme cases, it can cost less to distill a magic state than to perform a logical Clifford gate on full-distance logical qubits.
The evolution of stem-cell transplantation in multiple myeloma (2018)

Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure. The data concerning the timing of ASCT (early in the disease course or at first relapse), single <i>versus</i> tandem (double) ASCT and the role and duration of consolidation and maintenance therapy post ASCT remain conflicting. This review aims to discuss the evolution of stem-cell transplant over the past 3 decades and its current role in the context of newer, safer and more effective therapeutic agents.
Peptide transporter‐independent, stress protein‐mediated endosomal processing of endogenous protein antigens for major histocompatibility complex class I presentation (1994)

The peptide transporter-defective cell line RMA-S expressing the wild-type simian virus 40 large T antigen (wtT-Ag) from a transfected gene did not present two well-defined, H-2 class I (Db)-restricted epitopes of T-Ag to cytotoxic T lymphocytes (CTL). Hence, "endogenous" processing and presentation of the wtT-Ag depended on a functional peptide transporter heterodimer. In contrast, both T-Ag epitopes were efficiently presented to CTL by transfected RMA-S cells expressing a truncated, cytoplasmic T-Ag variant (cT-Ag) or a karyophilic, amino-terminal 272-amino acid T-Ag fragment. Transporter-independent "endogenous" processing of mutant T-Ag molecules correlated with their association with the constitutively expressed heat shock protein 73 (hsp73). Class I-restricted presentation of both epitopes processed from these hsp73-associated protein antigens was sensitive to NH4Cl and chloroquine. These data indicate that selected intracellular proteins access an alternative, hsp73-mediated pathway for class I-restricted presentation that operates independent of peptide transporters in an endosomal compartment.
Dark Quenched Matrix Metalloproteinase Fluorogenic Probe for Imaging Osteoarthritis Development in Vivo (2008)

The early detection of osteoarthritis (OA) is currently a key challenge in the field of rheumatology. Biochemical studies of OA have indicated that matrix metalloproteinase-13 (MMP-13) plays a central role in cartilage degradation. In this study, we describe the potential use of a dark-quenched fluorogenic MMP-13 probe to image MMP-13 in both in vitro and rat models. The imaging technique involved using a MMP-13 peptide substrate, near-infrared (NIR) dye, and a NIR dark quencher. The results from this study demonstrate that the use of a dark-quenched fluorogenic probe allows for the visual detection of MMP-13 in vitro and in OA-induced rat models. In particular, by targeting this OA biomarker, the symptoms of the early and late stages of OA can be readily monitored, imaged, and analyzed in a rapid and efficient fashion. We anticipate that this simple and highly efficient fluorogenic probe will assist in the clinical management of patients with OA, not only for early diagnosis but also to assess individual patient responses to new drug treatments.
Novel oxylipins formed from docosahexaenoic acid by potato lipoxygenase—10(S)‐hydroxydocosahexaenoic acid and 10,20‐dihydroxydocosahexaenoic acid (2005)

Potato tuber lipoxygenase (ptLOX) has been shown to catalyze the aerobic formation of at least four major oxygenated derivatives of DHA. Two of the products--7,17(S)- and 10,17(S)-dihydro(pero)xy-DHA [7,17- and 10,17-diH(P)DHA]--were formed from soybean 15-LOX-derived 17(S)-hydro(pero)xy-DHA [17(S)-H(P)DHA], whereas two novel oxylipin compounds--10(S)-hydro(pero)xy-DHA and 10,20-dihydro(pero)xy-DHA [10(S)-H(P)DHA and 10,20-diH(P)DHA, respectively]--were the major direct products of DHA oxidation by ptLOX. The reactions proceeded relatively slowly but could be stimulated by catalytic amounts of SDS. Micromolar concentrations of 10(S)-HPDHA effectively abolished the kinetic lag period of ptLOX activation. Enzymatic activity with DHA or 17(S)-HPDHA as substrate was about 8% of that with linoleic acid--a standard natural ptLOX substrate--whereas 17(S)-HDHA was converted at a rate of approximately 1%. The enzyme was relatively unstable and quickly inactivated during the reaction with DHA on with 17(S)-HPDHA (first-order kinetic constant of inactivation kin = 1.5 +/- 0.3 min(-1)), but not with 17(S)-HDHA. Both 7,17- and 10,20-diH(P)DHA were clearly products of double oxygenation catalyzed by soybean 15-LOX and/or ptLOX. Our observation that ptLOX could convert 17-HDHA to 10,17-diH(P)DHA indicates that this dihydroxylated derivative of DHA also can be formed via a double lipoxygenation mechanism.
Improving the action of insulin. (1995)

Improving the action of insulin is a relatively new concept in diabetes management. Insulin sensitivity can be improved by reduction of excessive body weight, regular physical activity and, possibly, by correcting a subclinical magnesium deficiency. Pharmacological means of improving insulin action include metformin, antiobesity serotoninergic agents and, possibly, benfluorex. New compounds aiming at improving the action of insulin are in development and include thiazolidinedione derivatives (known as "insulin sensitizers"), inhibitors of adipose tissue lipolysis (e.g. acipimox), and inhibitors of free fatty acid oxidation (e.g. etomoxir). Avoidance of drugs that reduce insulin sensitivity, such as beta blockers and thiazide diuretics, is recommended. Finally, cigarette smoking is associated with resistance to insulin but it remains to be demonstrated that cessation of cigarette smoking does in fact increase sensitivity to insulin.
Three‐color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood (2004)

Experiments described herein were designed to evaluate the performance characteristics of a flow cytometry-based system that scores the incidence of peripheral blood micronucleated reticulocytes (MN-RETs). These procedures represent the continued refinement of a previously reported anti-CD71-based method (Dertinger et al. [1996]: Mutat Res 371:283-292), with the following modifications: incorporation of a third fluorescent label to exclude platelets from the MN-RET region, and use of a CD71-associated fluorescence thresholding technique to increase data acquisition rates. Mouse, rat, and human blood samples were analyzed using both the previously described two-color procedure (anti-CD71-FITC and propidium iodide) and a newly developed three-color technique (which adds an antiplatelet-PE antibody). The rodent specimens were also evaluated by standard microscopy procedures (acridine orange staining). Mouse blood was collected via heart puncture of vehicle- and 5-fluorouracil-treated CD-1 mice; blood samples from saline-treated Sprague-Dawley rats were collected from the tail vein and via heart puncture. Rodent blood samples were analyzed by both the two- and three-color methods. Human blood specimens, obtained via arm venipuncture from cancer patients undergoing radiation therapy, were analyzed for MN-RETs using the two-color method. Subsequently, blood samples from a single chemotherapy patient were analyzed by both the two- and three-color methods. Finally, the chemotherapy patient blood samples and blood samples from 15 healthy volunteers were evaluated at very high densities in conjunction with a CD71-associated fluorescence thresholding technique. Results of these investigations showed that data from mouse blood analyzed by the two- and three-color procedures correlated well with microscopy data (r values = 0.917 and 0.937 for the two- and three-color methods, respectively); all three methods confirmed the genotoxicity of 5-FU. Data from rat tail vein samples showed improved reproducibility with the three-color technique, but no significant difference between the two techniques was seen with the heart puncture specimens. Human blood analyzed according to the two-color procedure produced unreliable results, as platelets and platelet aggregates impacted the rare MN-RET scoring region. The three-color technique effectively overcame this problem and produced reproducible measurements that fell within expected ranges. For human blood analyses, the high cell density/CD71-thresholding technique provided significant improvements over the low-density technique, as it allowed data acquisition to occur approximately six times faster with no loss of sensitivity.
Preparation of an Ionic Polymer Gel Microactuator and Measurement of Its Periodic Motions. (1997)

イオン性高分子ゲルを用いたマイクロアクチュエーターを作製し,その動作性能を調べ,100-500mVの低い電圧でゲルの膨潤収縮による運動を確認した.ゲル運動の応答速度は速く,0.4sの周期で,周期的に変動する電圧に追従して動くことが確かめられた.また,5時間以上の連続運転も可能であるが,ゲル中の水の蒸発による運動性の低下,および微小電極間における電気伝導性の物質の析出による電気的短絡により停止する.安定な運動を実現するためには,これらの問題点を解決することが必要である.
Digital neighborhood watch (2013)

In a neighborhood watch group, neighbors cooperate to prevent crime by sharing information and alerting police of suspicious activities. We propose a digital neighborhood watch (DNW) in which security cameras of individual homes work together to monitor the neighborhood. DNW could augment neighborhood watch by providing digital evidence of crime, increasing visibility of neighborhood activity, and automatically sending alerts when suspicious events occur. We investigate the appeal of sharing camera data with neighbors through semi-structured interviews with 11 households. Our participants validated the potential of sharing data with neighbors, particularly to provide evidence after an incident. But they also had security and privacy concerns about divulging their cameras' field of view and giving ongoing access to neighbors. For some participants, these concerns can be alleviated by enabling sharing of processed cameras views that include only the fore-ground activity or only public property (e.g., sidewalks).
Incidence of rhegmatogenous retinal detachments after intravitreal antivascular endothelial factor injections (2010)

The incidence of RD in our community setting was very low (1 per 7188 injections). All RD occurred during the early postoperative period. The risks of RD can be minimized by a careful injection technique.
THE ROLE OF ENDOTHELIAL CELLS IN INFLAMMATION (1990)

Departments of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts
Depression of Gelsolin Levels and Detection of Gelsolin-Actin Complexes in Plasma of Patients with Acute Lung Injury (1988)

Actin is the major protein of muscle and nonmuscle cells and is one of the most abundant body proteins. Physiologic or pathologic cell death may therefore result in the liberation of large amounts of this fibrous protein into the extravascular space. The potential for long actin filaments to increase plasma viscosity and change the rheology of the microvasculature are potentially obviated by the presence of 2 recently recognized plasma actin-binding proteins, vitamin-D-binding protein, and plasma gelsolin. As part of our initial evaluation of this newly recognized physiologic system in humans, we measured levels of gelsolin in plasma samples from patients with extensive lung injury. Gelsolin levels were depressed in 25 of 25 patients with the adult respiratory distress syndrome (ARDS), a disease characterized by massive cellular injury, as determined by either of 2 functional assays for gelsolin. Mean total gelsolin concentration of 20 patients with ARDS was 89.2 +/- 33 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001) and the mean free gelsolin concentration 69.6 +/- 29 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001). Gelsolin concentrations of 6 patients with bacterial pneumonias were also depressed, but to a lesser degree (mean total level, 117 +/- 21 micrograms/ml). Direct demonstration of the presence of actin in these plasmas (but not in normal plasmas) was performed by precipitating actin directly with DNase-Sepharose beads, or indirectly with antigelsolin-Sepharose beads, as confirmed with immunoblotting. Actin was found in 18 of 19 patients using DNase beads and in 7 of 19 using antigelsolin beads.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of a Chemical Plant Defense Mechanism in Grasses (1997)

In the Gramineae, the cyclic hydroxamic acids 2,4-dihydroxy-1, 4-benzoxazin-3-one (DIBOA) and 2,4-dihydroxy-7-methoxy-1, 4-benzoxazin-3-one (DIMBOA) form part of the defense against insects and microbial pathogens. Five genes, Bx1 through Bx5, are required for DIBOA biosynthesis in maize. The functions of these five genes, clustered on chromosome 4, were demonstrated in vitro. Bx1 encodes a tryptophan synthase alpha homolog that catalyzes the formation of indole for the production of secondary metabolites rather than tryptophan, thereby defining the branch point from primary to secondary metabolism. Bx2 through Bx5 encode cytochrome P450-dependent monooxygenases that catalyze four consecutive hydroxylations and one ring expansion to form the highly oxidized DIBOA.
Charge detection mass spectrometry: weighing heavier things (2017)

Charge detection mass spectrometry (CDMS) is a single molecule method where the mass of each ion is directly determined from individual measurements of its mass-to-charge ratio and charge. CDMS is particularly valuable for the analysis of high mass and heterogeneous analytes, where conventional MS methods are often confounded. In the last few years, CDMS has received a renaissance. Technical developments have improved the resolution and dramatically increased the breadth of problems that can be addressed. These improvements have moved CDMS more into the mainstream as interest in the application of mass spectrometry to high molecular weight species has grown. In the article, the three main variants of CDMS are described, along with an overview of recent applications.
Bone marrow stem cells in the infarcted heart (2005)

Conventionally, the heart is perceived as a terminally differentiated organ, which is incapable of regeneration. Adult stem cell transplantation is aimed at replenishing the myocyte number to compensate for the cardiomyocyte loss during the process of cardiomyocyte necrosis following infarction. More recently, the focus has been shifted on the use of autologous skeletal myoblasts and bone marrow derived stem cells. Here, we have reviewed some interesting aspects of the fast emerging field of bone marrow derived stem cell therapy for cardiac repair.
Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones (2005)

It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high-resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2-Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed.
Corneal Lymphangiogenesis (2003)

Antilymphangiogenic strategies may improve transplant survival both in the high- and low-risk setting of corneal transplantation.