gebhart/patrepeval huggingface dataset:
Motor Fluctuations in Levodopa Treatment: Clinical Pharmacology (1996)

Fluctuations in motor performance and dyskinesias are a common problem in the long-term management of Parkinson's disease. The pharmacokinetics and the pharmacodynamics of levodopa, loss of presynaptic dopamine terminals, alterations in postsynaptic dopamine receptor sensitivity, or changes in the modulatory influences of nondopaminergic transmitter system could play a pathogenic role. The short half-life of levodopa and its absorption and transport are important factors. The pharmacodynamic response to levodopa changes during long-term therapy. An absolute threshold in plasma levodopa level, below which the patients are off, appears. The patients show a therapeutic window for levodopa which becomes narrower with time. This therapeutic window can be widened by giving continuous infusion of dopaminergic drugs. Motor fluctuations can be ameliorated by a more physiological continuous stimulation of the receptor site and by avoiding repeated shifting in levodopa levels. Long-term complications are attenuated by an early combination of levodopa with dopamine agonist.
Antibody Targeting of TGF-&#946; in Cancer Patients (2011)

The role of TGF-β in tumor development and progression is complex. Genetic mutations that disrupt the antiproliferative signaling effects of TGF-β play a key role in the process of malignant transformation for many types of tumors. Paradoxically, this loss of sensitivity to TGF-β's inhibitory actions often leads to TGF-β overexpression by the tumor cells or by normal cells that are recruited to the tumor microenvironment. Elevated concentrations of TGF-β in the tumor microenvironment have been shown to facilitate tumor growth and metastasis. Numerous published studies have provided evidence that inhibition of TGF-β using antibodies, soluble receptors and small molecule inhibitors of TGF-β signal transduction can have beneficial effects in murine models of cancer. Given the pleiotropic nature of TGF-β and its homeostatic role in numerous biological processes, serious concerns have been expressed regarding the safety of administering TGF-β antagonists to human patients. Interestingly, the results of numerous animal toxicology studies of TGF-β antibodies in normal rodents and primates have shown that administration of neutralizing anti-TGF-β antibodies is well tolerated and any adverse effects were reversible or self-limiting. Likewise, administration of a human anti-TGF-β antibody (fresolimumab) in three separate human phase 1 clinical trials has also been shown to be well tolerated.
A Ring-Based Decentralized Collaborative Non-blocking Atomic Commit Protocol. (2008)

Many asynchronous distributed atomic commit protocols use a coordinator, either an application server or an elected database server, to handle the progress of a transaction. When the coordinator fails or the network becomes partitioned, the transaction may block or may suffer from a split brain syndrome. In this paper we propose a decentralized, collaborative, non-blocking atomic protocol, which piggybacks transaction statuses of all transaction participants onto tokens, and passes the tokens in a logical ring with two distinct directions. Each participant uses the information in the tokens to make a decision of when to go to the next state. Using the state vectors in the tokens, the transaction can progress even if the network is partitioned, and the protocol will ensure uniform agreement on success or failure of the transaction.
Leveraging Social-Network Infrastructure to Improve Peer-to-Peer Overlay Performance: Results from Orkut (2005)

Application-level peer-to-peer (P2P) network overlays are an emerging paradigm that facilitates decentralization and flexibility in the scalable deployment of applications such as group communication, content delivery, and data sharing. However the construction of the overlay graph topology optimized for low latency, low link and node stress and lookup performance is still an open problem. We present a design of an overlay constructed on top of a social network and show that it gives a sizable improvement in lookups, average round-trip delay and scalability as opposed to other overlay topologies. We build our overlay on top of the topology of a popular real-world social network namely Orkut. We show Orkuts suitability for our purposes by evaluating the clustering behavior of its graph structure and the socializing pattern of its members.
Polymorphism of the Apolipoprotein E Gene and Early Carotid Atherosclerosis Defined by Ultrasonography in Asymptomatic Adults (1997)

Clinical and autoptical studies have suggested a predisposing role of the allele E4 of apolipoprotein E (apoE) in the development of atherosclerosis and cardiovascular disease. To investigate the possible contribution of apoE allele polymorphism to the carotid intima-media thickness (IMT) as assessed by ultrasound, we studied 260 asymptomatic nondiabetic subjects (121 men, 139 women; mean +/- SD age, 53 +/- 7 years), randomly selected from the population register of the inhabitants of Trieste, Italy. B-mode ultrasound was used to quantify the maximum IMT at 12 sites on the near and far wall of the common, bifurcation, and internal carotid arteries. ApoE genotypes were determined from amplified apoE sequences by restriction isotyping. The frequencies of E2, E3, and E4 alleles were 0.073, 0.827, and 0.100, respectively. As expected, subjects with E4 allele had the highest levels of total serum cholesterol and LDL cholesterol, subjects with E2 allele had the lowest levels, and those with E3 genotype had intermediate levels. The echographic measurements of carotid IMT showed increasing values from E2 to E4 carriers. After adjustment for total and LDL cholesterol serum levels, triglycerides, ratio of LDL to HDL cholesterol, age, sex, and body mass index, ANCOVA showed that the common carotid IMT was significantly greater (P = .029) in subjects with E4 allele compared with E3 carriers. Our data confirm the influence of apoE4 on cholesterol levels and clearly show that apoE genotype affects carotid atherosclerosis in its early stages in middle-aged asymptomatic subjects.
Molecular study of the Prader‐Willi syndrome: Deletion, RFLP, and phenotype analyses of 50 patients (1991)

Deletion and RFLP studies with 5 cloned DNA markers localized at 15q11.2 were performed in 50 patients with the Prader-Willi syndrome (PWS). A one-copy density (deletion) for at least one of 4 loci, D15S9, D15S11, D15S10, D15S12, was detected in 32 (64%) of the 50 patients; deletions of each of the 4 loci were found in 29, 30, 29, and 28 patients, respectively. Three patients showed 4 or more copy density for D15S12 locus, in addition to deletions. The remaining 18 patients showed two-copy densities for each of the 4 loci. A common site of rearrangements among our 32 patients as well as the reported patients seemed to be confined to a segment between D15S9 and D15S11, suggesting the putative PWS gene locus in this segment. Of 6 patients who have cytologic deletions but did not show any molecular deletions, 3 have normal size of hands and feet, and 4 have normally pigmented skin and hair. The normal pigmentation was also observed in 3 patients who had small molecular deletions in the examined 5-locus segment. These observations may support the conception of contiguous gene syndrome. RFLP analysis demonstrated maternal uniparental isodisomy of chromosomes 15 in both a patient with 45,t(15q;15q) and a karyotypically normal patient. Based on the results of the present study, a new model is proposed to explain the occurrence of PWS with a variety of chromosome abnormalities, including partial monosomy, disomy, trisomy, and/or tetrasomy for 15q11.2. The normal development may require an even or more "number ratio" of paternally derived allele(s) to maternally derived allele(s) of the gene(s) localized at 15q11.2, and a disturbance of the ratio would lead to the PWS phenotype.
Theory of metal-insulator-semiconductor solar cells (1977)

Recent reports in the literature indicate that the introduction of an interfacial oxide layer in a Schottky barrier can greatly increase the photovoltaic conversion efficiency of such devices. We propose an explanation for the operation of such solar cells based on the concept that they are minority-carrier nonequilibrium MIS tunnel diodes. Calculations of efficiency as a function of insulator thickness, substrate carrier concentration, surfaces states, and oxide charge are presented. These indicate that a maximum theoretical efficiency of 21% is possible under AM2 illumination for high substrate doping and low interface defect density.
Protein secretion by enteropathogenic Escherichia coli is essential for transducing signals to epithelial cells. (1995)

Enteropathogenic Escherichia coli (EPEC), a major cause of pediatric diarrhea, adheres to epithelial cells and activates host cell signal transduction pathways. We have identified five proteins that are secreted by EPEC and show that this secretion process is critical for triggering signal transduction events in epithelial cells. Protein secretion occurs via two pathways: one secretes a 110-kDa protein and the other mediates export of the four remaining proteins. Secretion of all five proteins was regulated by temperature and the perA locus, two factors which regulate expression of other known EPEC virulence factors. Amino-terminal sequence analysis of the secreted polypeptides identified one protein (37 kDa) as the product of the eaeB gene, a genetic locus previously shown to be necessary for signal transduction. A second protein (39 kDa) showed significant homology with glyceraldehyde-3-phosphate dehydrogenase, while the other three proteins (110, 40, and 25 kDa) were unique. The secreted proteins associated with epithelial cells, and EaeB became resistant to protease digestion upon association, suggesting that intimate interactions are required for transducing signals.
A patent review of IDO1 inhibitors for cancer (2018)

This review demonstrates that the structural diversity of new IDO1 inhibitors could be expanded via a number of approaches.
Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. (1994)

The focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by cell adhesion receptor integrins and by neuropeptide growth factors. To gain insight into FAK function, we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains. We report here the stable association of FAK with phosphatidylinositol 3-kinase (PI3-kinase; EC 2.7.1.137) in NIH 3T3 mouse fibroblasts. This interaction was stimulated by cell adhesion concomitant with FAK activation. We also found that recombinant FAK bound to the p85 subunit of PI 3-kinase directly in vitro and that autophosphorylation of recombinant FAK in vitro increased its binding to PI 3-kinase. We detected increased tyrosine phosphorylation of the p85 subunit of PI 3-kinase during cell adhesion and observed direct phosphorylation of p85 by FAK in vitro. Together, these results suggest that PI 3-kinase may be a FAK substrate in vivo and serve as an effector of FAK.
Genetic Variations in Multiple Drug Action Pathways and Survival in Advanced Stage Non–Small Cell Lung Cancer Treated with Chemotherapy (2011)

Common genetic variations in genes of EGFR and glutathione pathways may be associated with overall survival among patients with advanced stage NSCLC treated with platinum, taxane, and/or gemicitabine combinations.
Measuring bond market liquidity: devising a composite aggregate liquidity score (2010)

The importance of liquidity in financial markets is emphasized strongly in the academic literature. There is no single definition of liquidity, which can lead to confusion when attempting to measure liquidity levels. This problem is often solved through the use of proxy indicators such as the bid offer spread. No single measure is completely satisfactory, and the use of proxy measures renders comparison across markets difficult. Our objective is to devise a composite aggregate measure of liquidity that makes use of a range of market factors, and which is applicable to any financial market. For illustration, we consider the UK government bond market during 1993–2002, a period during which structural reform aimed at improving liquidity was undertaken. We devise a transparent, accessible and easy-to-implement method to measure liquidity level in a financial market, using an aggregate scoring system. This adopts a composite methodology, using components selected on the basis of their relative importance to promoting liquidity. Our measure suggests that market liquidity improved in the gilt market our observation period. Furthermore, the measurement methodology we propose may be employed as a practical tool by institutional investors to measure liquidity in any financial market, and enables them to make comparisons across different markets prior to making the investment decision.
CD66 identifies a neutrophil-specific epitope within the hematopoietic system that is expressed by members of the carcinoembryonic antigen family of adhesion molecules (1991)

Preliminary results from the IVth Leucocyte Culture Conference have classified the monoclonal antibody (MoAb), YTH 71.3.2, as CD66. Two other MoAbs, YPC 2/12.1 and CE6/2D3.1, share a common cellular specificity, reacting with cells of the neutrophil series and colonic epithelium. The YTH 71.3.2 and CE6/2D3.1 MoAbs both recognize a similar CD66 defined epitope that is distinct from that identified by YPC 2/12.1. By Western blotting, these antibodies react with different molecular species from cells of different lineages. The antibodies identify 50- to 55-Kd, 80- to 100-Kd, and 130- to 200-Kd components present in a semi-purified carcinoembryonic antigen (CEA) preparation from colonic adenocarcinomas and a 90- to 130-Kd molecule from HL-60 cells. With the colonic cell line, LS174T, YPC2/12.1 stains diffuse bands of 160 to 200 Kd and 90 to 130 Kd with equal intensity, whereas the binding of CE6/2D3.1 and YTH 71.3.2 is biased toward the lower molecular weight set of molecules. Remarkably, all three antibodies recognize CEA-related molecules. Defined analyses using HeLa cells transfected with CEA, NCA(NCA-50/90), and CGM6(NCA-95) cDNAs show that the three MoAbs identify CEA to varying degrees. While YTH 71.3.2 and CE6/2D3.1 also bind to NCA-50/90, YPC 2/12.1 recognizes an epitope expressed by both the NCA-50/90 and NCA-95 molecular species.
Changes in fructose & citric acid in accessory glands of reproduction of rats following long-term treatment with isomers of clomiphene citrate. (1973)

The effects of 500 mcg/kg/day of cis- or trans-clomiphene for 60 days on the testis and accessory glands of reproduction in adult male rats and the pattern of recovery following withdrawal of treatment were described. In animals treated with cis-clomiphene, testis weights showed little change from those of controls except in Week 2 of recovery when testicular weights were significantly less than in controls (p.001). The weights of all the accessory glands were significantly less as compared with controls (p.001) at the termination of treatment but reached control levels by the end of the 4 week recovery period. Citric acid (seminal vesicles and ventral prostate) and fructose (dorsolateral prostate and coagulating glands) levels decreased significantly in Week 2 compared with controls (p.001) but were restored to normal by Week 4. Epididymal spermatozoa were nonmotile at the end of treatment as well as in Week 1 of recovery; none of the treated males mated. Spermatozoa motility and normal mating behavior were restored by Weeks 3 and 4 of recovery. In rats treated with trans-clomiphene testes and accessory glands and their secretory activity (citric acid and frutose) were reduced significantly (p.001) and returned to control levels by Week 4 of recovery. Epididymal spermatozoa were nonmotile at the end of treatment and during the first 2 weeks of recovery but returned to normal during Week 3 of recovery along with normal mating behavior. The observed inhibitory effects on the testes and accessory glands may be due to estrogenicity of the compounds modifying the synthesis and/or release of gonadotropins mediated through the hypothalamo-hypophyseal axis. Complete recover, as evidenced by birth of normal young within 30 days of treatment withdrawal, suggests that the effects of these compounds are transient in adult male rats. The trans-isomer seemed to be more estrogenic than the cis-isomer.
Phase I trial of alvespimycin (KOS-1022; 17-DMAG) and trastuzumab (T) (2007)

1115 Background: Alvespimycin (A) inhibits the activity of Hsp90, resulting in degradation of client proteins, such as the HER2 receptor. In vivo, Hsp90 inhibition induces rapid degradation of HER2 with loss of pAKT, cyclin D2 and tumor growth inhibition. Methods: Pts receive standard weekly doses of T followed by A in escalating doses via IV doses over 1 hr. Define the recommended dose (RP2D), toxicity and signs of activity of T+A in pts with solid tumors. PK: assessed after the 1 st and 4 th infusion. PBLs: purified to investigate changes in intracellular signaling proteins by immunoblot. The RP2D will produce DLT in no more than 1/6 evaluable pts. Results: 21 pts enrolled in 3 cohorts (60, 80 and 100 mg/m 2 ). Median age 53 yrs, range 31–75; median KPS 90; prior regimens not including hormonal therapy: median 6, range 1–13; prior T-regimens for MBC pts: median 3, range 0–9. Diagnoses: HER2+ MBC (n=18), ovarian (n=3). DLT was observed at the highest dose, consisting of 1 pt with hypoxia and ↓LVEF; an additional pt at this dose had Grade 3 ↑AST, however ↑hepatic metastases and ascites were observed. Drug-related toxicity: diarrhea (60%), fatigue, headache (both 45%), nausea, arthralgias (both 40%), dry eye and pain in extremity (both 25%); all Grade 1–2 severity except 1 episode of Gr3 fatigue and Gr3 diarrhea. PK (n=18): t½ 17.7 hr (32%CV); Clearance 18.1 L/hr (46%CV); Vz 438L (42%CV); no change upon weekly dosing. AUC inf /C max (100 mg/m 2 ): 14268 ng*hr/mL (60%CV) and 2233 ng/mL (23.5%CV). HER2+ MBC activity: 1 pt (13 prior regimens; 3x T and 1x lapatanib) with evaluable disease showed near complete resolution of lung metastases by CT/PET with significant improvement in dyspnea; 3 pts with HER2+ MBC with SD (4, 5 and 7+ months). Ovarian CA activity: 1 pt (HER2 unknown; 13 prior regimens; 11+ months on-study) with evaluable disease showed near complete resolution of ascites and pleural effusion at end of Cycle 2 with ↓83% CA125. Dose-dependent increase in Hsp70 in PBLs; at 80 and 100 mg/m 2 , Hsp70 induction was maintained prior to successive weekly doses. Conclusions: Combination of T+A has signs of activity in H-refractory HER2+ MBC and refractory ovarian cancer. Definition of RP2D dose is pending. Toxicity has been manageable. No significant financial relationships to disclose.
Protein printing with an atomic force sensing nanofountainpen (2003)

We demonstrate the direct printing of proteins on a surface using a cantilevered nanopipette as the probe of a scanned probe microscope. Protein features as small as ∼200 nm were directly delivered through the ∼100 nm aperture of the nanopipette by simply contacting the probe with any surface. This allows for the direct connection of this methodology to standard separation techniques so that multiple proteins can be printed through one nanopipette at different locations in ambient conditions.
Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress. (2005)

Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestine and brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin and is stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidase IV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone. Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomical status of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulin release and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacement in diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesis of type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to some extent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers as an anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basal and stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanisms may participate in the pathogenesis of the most common metabolic and behavioral disorders.
Precision Polymers and 3D DNA Nanostructures: Emergent Assemblies from New Parameter Space (2014)

Polymer self-assembly and DNA nanotechnology have both proved to be powerful nanoscale techniques. To date, most attempts to merge the fields have been limited to placing linear DNA segments within a polydisperse block copolymer. Here we show that, by using hydrophobic polymers of a precisely predetermined length conjugated to DNA strands, and addressable 3D DNA prisms, we are able to effect the formation of unprecedented monodisperse quantized superstructures. The structure and properties of larger micelles-of-prisms were probed in depth, revealing their ability to participate in controlled release of their constituent nanostructures, and template light-harvesting energy transfer cascades, mediated through both the addressability of DNA and the controlled aggregation of the polymers.
Extraction of extracellular polymeric substances (EPS) from biofilms using a cation exchange resin (1995)

A cation exchange resin was used to extract water soluble EPS material from different sewer biofilms and a biofilm monoculture of P.putida. The extraction method seemed to be especially suitable for extracting humic substances and proteins from biofilms but also carbohydrate could be extracted, depending on the nature of the sample. Extraction conditions must be well defined because the extraction efficiency was dependent on stirring intensity, amount of cation exchange resin and extraction time. Up to 20% of the total biofilm protein was found in the DOWEX-extractable fraction. No significant cell-lysis up to 2 hours of extraction time could be detected by acridine orange (AO) direct counts. The same was true when applying the extraction method to a batch culture of P.putida. However, the number of viable cells in the batch culture as recorded by plate count technique was reduced to 28 % after 30 min of extraction. In conclusion, proteins and humic substances can be extracted from biofilm EPS in considerable amounts and should be investigated more in detail when analysing the properties of the EPS matrix of a biofilm.