gebhart/patrepeval huggingface dataset:
FOLFIRI regimen as second-/third-line chemotherapy in patients with advanced pancreatic adenocarcinoma refractory to gemcitabine and platinum salts: A retrospective series of 70 patients. (2011)

272 Background: Gemcitabine-based regimen is a standard of first-line chemotherapy in patients with advanced pancreatic adenocarcinoma (PAC) and 5-FU/oxaliplatin combination is an option for second line (Oettle, 2009). Some data suggest a potential efficacy of 5-FU/irinotecan regimen (FOLFIRI) as first-line treatment (Taïeb, 2007)or in patients with gemcitabine/platinum-refractory advanced PAC (Yoo, 2009; Gebbia, 2010). Methods: All consecutive patients with unresectable advanced PAC (01-2005/05-2010) and OMS≤2 received FOLFIRI-1 (irinotecan 180 mg/m 2 D1, n=60) or FOLFIRI-3 regimen (irinotecan 100 mg/m 2 D1/D3 n=10) after failure of gemcitabine- and platinum-based chemotherapies as a systematic policy in two institutions. Following data were analyzed: tumor response, progression free survival (PFS), overall survival rate (OS), and grade 3-4 toxicities. Results: Seventy patients were studied. Median age was 60 years (range: 24-81); 37 (52.9%) were male; 30 (42.9%) were PS 0, 27 were PS 1 and 13 were PS 2. Cancer was locally advanced in 15.7% and metastatic in 84.3% of patients. Before FOLFIRI regimen, patients received 1 line (n=24, 34.3%), 2 lines (n=40, 57.1%) or ≥ 3 lines (n=6, 8.8%) chemotherapy. PFS with previous line was less than 3 months in most patients. Tumor control was achieved in 31 (44.3%) patients (partial response: 5, stable disease: 26). PFS was 17% at 12 months and 3% at 24 months. Median PFS was 23 weeks (range: 2-147). OS was 24% at 12 months and 9% at 24 months. Median OS was 24 weeks (range: 2-147). From the initial diagnosis, 1-year and 2-year survivals were 79% and 32%. Dose adaptation was required in 21 (30.0%) patients. Eighteen (25.7%) patients had grade 3-4 toxicities, mainly hematologic (n=13) or digestive (n=6). Febrile neutropenia occurred in 3 patients without death. Conclusions: FOLFIRI regimen after failure of gemcitabine- and platinum-based regimens for advanced PAC in our study had an acceptable toxicity and a surprising efficacy in patients OMS 0-2. These results suggest that FOLFIRI regimen should be further tested as first-line chemotherapy in patients with advanced pancreatic cancer. No significant financial relationships to disclose.
Effect of Temperature on 3rd Larval Ecdysis after Application of Light Stimuli in the Silkworm, Bombyx mori (1991)

To study the involvement biological rhythm in larval ecdysis in the 3rd instar of the silkworm, the effect of temperature on the process occurring between light-off stimuli and the next ecdysis was examined. Temperature after a light pulse affected the sequential endocrine processes of ecdysis in 3rd instar silkworm larvae. There was no difference in the timing of the "head critical period" after the light pulse between larvae reared at 30°C and 26°C, but those in the 22°C group reached this stage much later. In spite of this lack of difference in the time of the "head critical period" between the 26°C and 30°C groups, the patterns of increase in haemolymph ecdysteroids and the time of the "thorax critical period" showed marked difference.
Transtympanic endoscopy of the middle ear (1992)

Modern optical technology has made available fiberoptic and rigid endoscopes with diameters of 2 mm and less with acceptable resolution. Endoscopes of small caliber were introduced through a strategically placed myringotomy or an existing perforation to perform exploration of the middle ear as an in-the-office procedure. This technique is now routinely used as an adjunct in the diagnostic evaluation of patients with suspected middle ear conditions. Exploratory surgery of the middle ear may be avoided or definitive procedures may be planned better based on endoscopic findings.
Brain Natriuretic Peptide in Hypertension. (1995)

Brain natriuretic peptide (BNP) was first identified in the porcine brain and later isolated from porcine, rat, and human hearts. In humans, plasma BNP concentrations are progressively elevated with increasing severity of hypertension, particularly when left ventricular hypertrophy (LVH) is present. This presumably reflects increases in ventricular mass associated with increased synthesis and constitutive secretion of BNP from ventricular tissue. In this report, plasma BNP may be a marker for hypertensive LVH. Acute administration of BNP induces significant natriuresis and suppresses plasma aldosterone in hypertensive subjects. However, further studies are necessary to clarify the pathophysiological significance of BNP in essential hypertension.
Kinetics Tuning of Li-Ion Diffusion in Layered Li(NixMnyCoz)O2 (2015)

Using ab initio calculations combined with experiments, we clarified how the kinetics of Li-ion diffusion can be tuned in LiNixMnyCozO2 (NMC, x + y + z = 1) materials. It is found that Li-ions tend to choose oxygen dumbbell hopping (ODH) at the early stage of charging (delithiation), and tetrahedral site hopping (TSH) begins to dominate when more than 1/3 Li-ions are extracted. In both ODH and TSH, the Li-ions surrounded by nickel (especially with low valence state) are more likely to diffuse with low activation energy and form an advantageous path. The Li slab space, which also contributes to the effective diffusion barriers, is found to be closely associated with the delithiation process (Ni oxidation) and the contents of Ni, Co, and Mn.
Structure Determination of an Endogenous Sleep-Inducing Lipid, cis-9-Octadecenamide (Oleamide):  A Synthetic Approach to the Chemical Analysis of Trace Quantities of a Natural Product (1996)

The pursuit of endogenous sleep-inducing substances has been the focus of an extensive, complicated body of research. Several compounds, including Δ-sleep-inducing peptide and prostaglandin D2, have been suggested to play a role in sleep induction, and yet, the molecular mechanisms of this physiological process remain largely unknown. In recent efforts, the cerebrospinal fluid of sleep-deprived cats was analyzed in search of compounds that accumulated during sleep deprivation. An agent with the chemical formula C18H35NO was found to cycle with sleep−wake patterns, increasing in concentration with sleep deprivation and decreasing in amount upon recovery sleep. Since the material was generated in minute quantities and only under the special conditions of sleep deprivation, efforts to isolate sufficient material for adequate characterization, structure identification, and subsequent detailed evaluation of its properties proved unrealistic. With the trace amounts of the impure endogenous compound available, extensive MS studies on the agent were completed, revealing key structural features of the molecule including two degrees of unsaturation, a long alkyl chain, and a nitrogen substituent capable of fragmenting as ammonia. Additionally, HPLC traces suggested a weak UV absorbance for the unknown material. With this data in hand and encouraged by the relatively small size of the molecule, MW = 281, a synthetic approach toward the structural identification of the natural compound was initiated. Herein, we report the full details of the synthesis and comparative characterization of candidate structures for this endogenous agent that led to the unambiguous structural correlation with synthetic cis-9-octadecenamide.
Characterization of the human p53 gene. (1986)

Cosmid and lambda clones containing the human p53 gene were isolated and characterized in detail. The gene is 20 kilobases (kb) long and has 11 exons, the first and second exons being separated by an intron of 10 kb. Restriction fragments upstream of sequences known to be within the first identified exon were tested for promoter activity by cloning them in front of the chloramphenicol acetyltransferase gene and transfecting the resulting constructs into HeLa cells. A 0.35-kb DNA fragment was identified that had promoter activity. Results of primer extension experiments indicated that the mRNA cap site falls within this fragment, as expected. Analysis of the sequence upstream of the presumptive cap site indicated that the human p53 promoter may be of an unusual type.
Custom Adeno-Associated Virus Capsids: The Next Generation of Recombinant Vectors with Novel Tropism (2005)

Recombinant gene delivery vehicles based on adeno-associated virus (rAAV) have emerged as promising vectors for the correction of genetic and acquired human disease states. These vectors possess many characteristics, including low pathogenicity and immunogenicity, and long-term gene expression after a single administered dose, that make them leading candidates for clinical gene therapy applications. Yet, the broad tissue tropism of the available AAV serotypes remains a disadvantage for the safest, most effective in vivo delivery of transgenes to target tissues. In addition, clinically relevant cell types exist that are poorly transduced by current rAAV vectors. As a result, increased efforts are now being made to tailor the tropism of rAAV to improve their transduction and selectivity profiles. Flexible, diverse methodologies have emerged that allow more control over the cell surface receptors rAAV employs for cell entry. These novel rAAV production strategies have resulted in unique vectors characterized by unique capsid protein sequences that employ alternative receptors, and have provided a better understanding of many basic aspects of the rAAV life cycle. This review aims to summarize the genetic methods currently being employed to customize rAAV capsids.
Experimental evolution of Ebg enzyme provides clues about the evolution of catalysis and to evolutionary potential (1999)

The ebg (evolved β-galactosidase) operon of Escherichia coli has been used since 1974 as a model system to dynamically study the evolutionary processes which have led to catalytic efficiency and substrate specificity in enzymes. Wild-type ebg β-galactosidase, encoded by ebgA, is a catalytically feeble enzyme that does not hydrolyze lactose or other β-galactosides efficiently enough to permit growth on those substrates. Each of two specific base substitutions at widely separated sites increases catalytic activity sufficiently to permit growth, and the combination of the two mutations further increases catalytic effectiveness and expands the substrate range of the enzyme in a non-additive fashion. Experimental studies suggested that in the 3126 bp coding region those two substitutions were the only mutations capable of increasing activity toward lactose sufficiently to permit growth. Alignment of EbgA with the LacZ β-galactosidase showed that both mutations were in active site amino acids. Multiple alignment and phylogenetic analysis of EbgA, LacZ, and 12 other related β-galactosidases showed that EbgA and LacZ diverged from a common ancestor at least 2.2 billion years ago, that they belonged to different subclasses of the family of 14 β-galactosidases, that the two subclasses differed at 12 of the 15 active site residues, and confirmed that the two previously identified mutations in ebgA are the only ones that can lead to enzyme with sufficient activity on lactose to permit growth. Studies of the catalytic mechanism of Ebg β-galactosidase have allowed the widely accepted Albery and Knowles model for the evolution of catalysis to be rejected.
A novel, low-cost implementation of "democratic" load-current sharing of paralleled converter modules (1996)

A simple, low-cost, and robust "democratic" (autonomous) current-sharing (CS) circuit is proposed and analyzed. The circuit maintains good CS among the modules by properly adjusting the voltage references of the modules based on the differences between the average current of the paralleled modules and the currents of the individual modules. Design guidelines for achieving a desired CS performance are given and verified on a number of DC/DC modules operating in parallel.
Mutations in NFKB2and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies (2014)

We confirm previous findings that mutations near the C-terminus of NFKB2 cause combined endocrine and immunodeficiencies. De novo status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed NFKB2 super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in Lym1 mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function.
Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function (2015)

Previously, we have demonstrated that the transplantation of viable, structurally intact, respiration competent mitochondria into the ischemic myocardium during early reperfusion significantly enhanced cardioprotection by decreasing myocellular damage and enhancing functional recovery. Our in vitro and in vivo studies established that autologous mitochondria are internalized into cardiomyocytes following transplantation; however, the mechanism(s) modulating internalization of these organelles were unknown. Here, we show that internalization of mitochondria occurs through actin-dependent endocytosis and rescues cell function by increasing ATP content and oxygen consumption rates. We also show that internalized mitochondria replace depleted mitochondrial (mt)DNA. These results describe the mechanism for internalization of mitochondria within host cells and provide a basis for novel therapeutic interventions allowing for the rescue and replacement of damaged or impaired mitochondria.
Hybridization selections, using immobilized driver DNA, to enrich for clones unique to a library. (1991)

We have developed a technique which allowed us to isolate sex-specific repeats of chickens (Gallus g. domesticus) from a genomic library originally containing one sex-specific repeat clone per 300 clones. Using this plus/minus selection method, we were able to enrich a sub-library in which the sex-specific repetitive clones made up over half of the population (170-fold increase in representation). This enrichment technique used hybridization kinetics to collect clones which are bound (plus selection) or not bound (minus selection) to their respective driver DNAs immobilized on nitrocellulose paper. Plus selections enriched for repetitive sequences and removed from the library most unique sequences as well as vectors containing no inserted sequences. These plus-selected sub-libraries were enriched for repetitive clones, yet still contained sequences representing as little as 10(-4) of the genome. Minus selection removed repetitive sequences shared between the driver and the library. When a plus-selected sub-library was minus selected, the doubly selected sub-library was enriched in repetitive sequences present in the library but not the minus driver.
Diastolic Stiffness of the Failing Diabetic Heart (2007)

Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal.
Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation (2006)

H2S is highly toxic and selectively inhibits butyrate oxidation in colonocytes. Ineffective detoxification may result in mucosal insult, inflammation, and ultimately in colorectal cancer (CRC). Rhodanese can detoxify H2S and is comprised of two isoenzymes: thiosulfate sulfurtransferase (TST) and mercaptopyruvate sulfurtransferase (MST). Using specific antisera to discriminate TST from MST, we found that only TST could detoxify H2S. In sections of normal colon, both enzymes were located on the luminal mucosal surface, and they were expressed in the colonocytes but not in the mucin-secreting goblet cells. Expression of both enzymes was focally lost in ulcerative colitis and markedly reduced in advanced colon cancer, the disease progression correlating with the decreased expression of MST and TST. In HT-29 cells, a human colon cancer cell line, TST activity and expression were significantly increased by butyrate and by histone deacetylase inhibition, agents that promote HT-29 cell differentiation. Sulfide (0.1 mM) also increased TST activity, but higher sulfide concentrations (0.3-3 mM) were toxic. Preincubation in butyrate to increase TST expression, decreased sensitivity of the cells to sulfide toxicity. We conclude that decreased expression of TST (or MST) is a tumor marker for CRC. TST expression is increased in colonocyte differentiation. Dysregulation of TST expression and activity resulting in inability to effectively detoxify could be a factor in the cell loss and inflammation that accompany ulcerative colitis and ultimately then in CRC.
The antimicrobial effects of glucosinolates and their respective enzymatic hydrolysis products on bacteria isolated from the human intestinal tract (2009)

This the first major in vitro study demonstrating the potential of these natural dietary chemicals as an alternative to, or in combination with, current antibiotic-based therapies for treating infectious diseases.
Structure-Based Design:  Potent Inhibitors of Human Brain Memapsin 2 (β-Secretase) (2001)

Memapsin 2 (beta-secretase) is one of two proteases that cleave the beta-amyloid precursor protein (APP) to produce the 40-42 residue amyloid-beta peptide (Abeta) in the human brain, a key event in the progression of Alzheimer's disease. On the basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and designed potent memapsin inhibitors. Structure-based design and preliminary structure-activity studies have been presented.
Tissue Factor Pathway Inhibitor Inhibits Aortic Smooth Muscle Cell Migration Induced by Tissue Factor/Factor VIIa Complex (1997)

Tissue factor (TF), a transmembrane glycoprotein, forms a high affinity complex with factor VII/VIIa (FVIIa) and thereby initiates blood coagulation. Tissue factor pathway inhibitor (TFPI) is an endogenous protease inhibitor of TF/FVIIa-initiated coagulation. We previously reported that TF was a strong chemotactic factor for cultured vascular smooth muscle cells (SMCs). In this study, we examined the contribution of FVIIa and the effect of TFPI to TF-induced cultured SMC migration. TF/FVIIa complex showed a strong migration ability, however, neither TF alone nor FVIIa induced SMC migration. TF/FVIIa treated by a serine protease inhibitor and the complex of TF and inactivated FVIIa (DEGR-FVIIa) did not stimulate SMC migration. Pretreatment with hirudin and the antibodies to alpha-thrombin and factor X had no effect on TF/FVIIa-induced SMC migration, although alpha-thrombin and factor Xa also induced SMC migration respectively. TFPI markedly inhibited TF/FVIIa-induced SMC migration in a concentration-dependent manner, but did not affect the SMC migration induced by platelet-derived growth factor (PDGF)-BB, basic fibroblast-growth factor (bFGF), or alpha-thrombin. These results indicate that the catalytic activity of TF/FVIIa complex is important on SMC migration, and TFPI can reduce SMC migration as well as thrombosis.
Introduction to Probability and Mathematical Statistics. (1988)

Probability Random Variables and Their Distributions Special Probability Distributions Joint Distributions Properties of Random Variables Functions of Random Variables Limiting Distributions Statistics and Sampling Distributions Point Estimation Sufficiency and Completeness Interval Estimation Test of Hypotheses Contingency Tables and Goodness-of-Fit Nonparametric Methods Regression and Linear Models Reliability and Survival Distributions Answers to Selected Exercises.
GermlineBRCAMutations Denote a Clinicopathologic Subset of Prostate Cancer (2010)

BRCA2 mutation carriers had an increased risk of prostate cancer and a higher histologic grade, and BRCA1 or BRCA2 mutations were associated with a more aggressive clinical course. These results may have implications for tailoring clinical management of this subset of hereditary prostate cancer.
Atg9 Trafficking in YeastSaccharomyces cerevisiae (2007)

Autophagy can be divided into selective and nonselective modes. This process is considered selective when a precise cargo is specifically and exclusively incorporated into autophagosomes, the double-membrane vesicles that are the hallmark of autophagy. In contrast, during nonselective, bulk autophagy, cytoplasmic components are randomly enwrapped into autophagosomes. To date, approximately 30 autophagy-related genes called ATG have been identified. Sixteen of them compose the general basic machinery catalyzing the formation of double-membrane vesicles in all eukaryotic cells. The rest of them are often not conserved between species and cooperate with the basic Atg proteins during either selective or nonselective autophagy. Atg9 is the only integral membrane component of the conserved Atg machinery and appears to be a crucial organizational element. Recent studies in the S. cerevisiae have shown that Atg9 transport is differentially regulated depending on the autophagy mode. In this addendum, we will review and discuss what has recently been unveiled about yeast S. cerevisiae Atg9 trafficking, its modulators and its potential role in double-membrane vesicle biogenesis.
From spawning grounds to the estuary: using linked individual‐based and hydrodynamic models to interpret patterns and processes in the oceanic phase of Atlantic menhaden Brevoortia tyrannus life history (1999)

Present theory suggests that population regulation in marine fishes cannot be resolved until an understanding of the processes involved in shaping the overall distribution (the number of populations, geographical extent, mean abundance and temporal changes in abundance) is developed. Here, we present a step toward understanding Atlantic menhaden population patterns, by studying processes in the Middle and South Atlantic Bights, which shape those patterns. We use individual‐based and hydrodynamic models to reinterpret the ‘mechanics’ of the menhaden life history, and put forward several potentially testable hypotheses. The success of the menhaden reproductive strategy seems to depend on the seasonal changes in the mean flow field of the Middle and South Atlantic Bights, suggesting that their life history may have been strongly structured by the regional physics of the system. Because the annual menhaden migration is size‐based and spawning occurs throughout the population’s range, the size distribution of the adult population may influence the supply of larvae to particular estuaries along the coast. Recruitment of larvae into Delaware and Chesapeake Bays may be dependent on spawning to the north of the bays’ mouths, owing to coastline shape and orientation in the vicinity of the bays. Our results suggest that management of this resource might be improved by consideration of the spatial and temporal variability in both the biological and the physical system.