gebhart/patrepeval huggingface dataset:
T140 analogs as CXCR4 antagonists identified as anti‐metastatic agents in the treatment of breast cancer (2003)

A chemokine receptor, CXCR4, and its endogenous ligand, stromal cell-derived factor-1 (SDF-1), have been recognized to be involved in the metastasis of several types of cancers. T140 analogs are peptidic CXCR4 antagonists composed of 14 amino acid residues that were previously developed as anti-HIV agents having inhibitory activity against HIV-entry through its co-receptor, CXCR4. Herein, we report that these compounds effectively inhibited SDF-1-induced migration of human breast cancer cells (MDA-MB-231), human leukemia T cells (Sup-T1) and human umbilical vein endothelial cells at concentrations of 10-100 nM in vitro. Furthermore, slow release administration by subcutaneous injection using an Alzet osmotic pump of a potent and bio-stable T140 analog, 4F-benzoyl-TN14003, gave a partial, but statistically significant (P</=0.05 (t-test)) reduction in pulmonary metastasis of MDA-MB-231 in SCID mice, even though no attempt was made to inhibit other important targets such as CCR7. These results suggest that T140 analogs have potential use for cancer therapy, and that small molecular CXCR4 antagonists could potentially replace neutralizing antibodies as anti-metastatic agents for breast cancer.
Knowledge-based approaches in the design and selection of compound libraries for drug discovery. (2002)

In the past decade, the pharmaceutical industry has realized the increasing significance of impacting the early phase hit-to-lead development in the drug discovery process. In particular, knowledge-based approaches emerged and evolved to address a multitude of issues such as absorption, distribution, metabolism and excretion (ADME), potency, toxicity and overall drugability. Each of these approaches seeks to bring together all relevant pieces of information and create a knowledge-oriented process to deploy such information in drug discovery. This review focuses on work relating to drugability, which aims at obtaining hits (or leads) that have enhanced likelihoods of leading to successful clinical candidates by medicinal chemistry efforts. The period covered in this review is from 1997 (since the publication of Lipinski's rule of 5) to March 2002.
AMINO ACID SEQUENCE OF SALMON ULTIMOBRANCHIAL CALCITONIN (1969)

Salmon ultimobranchial calcitonin has been isolated and rendered pure, as demonstrated by several chemical criteria. Its amino acid sequence was determined by means of manual Edman degradation of the intact molecule and of several peptide subfragments. Results of automated degradation provided confirmation of the structure. The salmon molecule possesses, in common with other calcitonins, a 32-amino acid peptide chain terminating in prolinamide and containing half-cystine residues at positions 1 and 7. Although the sequence of the salmon hormone differs considerably from that of the porcine, bovine and human calcitonins, the four hormones are homologous in 9 of 32 positions. The much higher biological potency possessed by the salmon calcitonin makes it of particular interest for future structure function studies.
A Review of Efficacious Technology-Based Weight-Loss Interventions: Five Key Components (2010)

Short-term results of technologically driven weight-loss interventions using these components have been promising, but long-term results have been mixed. Although more longitudinal studies are needed for interventions implementing these five components, the interface of technology and behavior change is an effective foundation of a successful, short-term weight-loss program and may prove to be the basis of long-term weight loss.
Textbook of the autoimmune diseases (2000)

I: Overview Autoimmunity: Basic Mechanisms Autoimmune Disease: Pathogenesis II: Autoimmune Disease and Organ Systems III: the Systemic Autoimmune Diseases Diseases of Unknown Etiology Associated with Infection Possible Autoimmune Syndromes Diagnosis Environmental Autoimmunity Experimental Autoimmune Syndromes Future Therapy of Autoimmune Disease Index
The Nuclear Factor YY1 Suppresses the Human Gamma Interferon Promoter through Two Mechanisms: Inhibition of AP1 Binding and Activation of a Silencer Element (1996)

Our group has previously reported that the nuclear factor Yin-Yang 1 (YY1), a ubiquitous DNA-binding protein, is able to interact with a silencer element (BE) in the gamma interferon (IFN-gamma) promoter region. In this study, we demonstrated that YY1 can directly inhibit the activity of the IFN-gamma promoter by interacting with multiple sites in the promoter. In cotransfection assays, a YY1 expression vector significantly inhibited IFN-gamma promoter activity. Mutation of the YY1 binding site in the native IFN-gamma promoter was associated with an increase in the IFN-gamma promoter activity. Analysis of the DNA sequences of the IFN-gamma promoter revealed a second functional YY1 binding site (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer activity was suppressed by YY1. Since the nuclear level of YY1 does not change upon cell activation, our data support a model that the nuclear factor YY1 acts to suppress basal IFN-gamma transcription by interacting with the promoter at multiple DNA binding sites. This repression can occur through two mechanisms: (i) cooperation with an as-yet-unidentified AP2-like repressor protein and (ii) competition for DNA binding with the transactivating factor AP1.
GM REVS UP '86 MANUFACTURING (1985)

General Motors' two newest plants, Buick City in Flint and Detroit-Hamtramck, show how serious GM is about Japanese-like manufacturing efficiencies and world-class quality levels. Buick City is probably the first assembly plant anywhere which is connected electronically to all of its suppliers. Detroit-Hamtramck may be the first modern American assembly plant to thrive without rail delivery. Details on each plant's operations are provided in this article.
A method to extract gate-bias-dependent MOSFET's effective channel width (1991)

A modification to the conventional channel conductance method is introduced to extract the MOSFET's effective channel width W/sub eff/. The gate-bias-dependent effective channel width can be readily delineated with this extraction method. The physical meaning of this gate-bias dependence is further discussed, and structures with different isolation configurations are studied. W/sub eff/ is influenced by the local oxide thickness, surface doping concentration, and gate voltage. Unless the transition between the channel active area and field isolation area is so abrupt that changes of both oxide thickness and doping concentration are like step functions, gate-bias dependence of W/sub eff/ will be inevitable. As gate bias increases in the strong inversion region larger gate bias will gradually turn on the transition region. This in turn increases the W/sub eff/. A strong or weak gate-voltage dependence of W/sub eff/ is indicative to a gradual or fast transition in doping concentration and oxide thickness from channel to the field regions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Measurement of the phase noise characteristics of an unlocked communications channel identifier (2002)

The authors review the technique of phase noise stability measurement using complex demodulation and the approach to an unlocked spread spectrum communications probe. This system has recently been developed to characterize a transhorizon communications channel at 11.6 GHz under both tropospheric scatter and anomalous propagation conditions. The receiver has a bandwidth of 31.25 MHz but has no carrier recovery and therefore no absolute phase reference. However, provided that the phase jitter and the frequency drift are small enough during the channel measurement period, it is possible to obtain an accurate channel transmittance estimate. The system has the capability of implementing time-domain signal averaging "on the fly", thus permitting high-speed channel identification under low SNR regimes. As the averaging period is increased (to improve the SNR), low phase jitter in the oscillators becomes imperative. The SNR improvement achieved is thus controlled by the maximum averaging period, which is a direct reflection of the stability of the oscillators.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A label-free high throughput resistive-pulse sensor for simultaneous differentiation and measurement of multiple particle-laden analytes (2006)

We describe an all-electronic, label-free, resistive-pulse sensor that utilizes multiple microchannels for parallel detection, counting and differentiation of multiple biological particles simultaneously. Four particle solutions, including 20 µm and 40 µm polymethacrylate particles, Juniper Scopulorum (Rocky Mountain Juniper) pollen and Populus deltidoes (Eastern Cottonwood) pollen, were loaded to the four peripheral reservoirs, respectively, and were driven to the central reservoir through four microchannels, all operating simultaneously for particle detection and counting. Experiments demonstrated that this sensor was able to differentiate and count multiple particle solutions simultaneously through its four microchannels fabricated on polymer membranes. Thus the sensing throughput has been improved significantly in contrast to typical Coulter counters without sacrificing accuracy, sensitivity and reliability. Furthermore, the experimental results also proved the feasibility of differentiating various pollens from polymethacrylate microparticles with the multi-channel resistive-pulse sensor. The differentiation is based on difference in size and surface charge for the bioparticles, with no need for labeling of samples. Possible improvements and extensions to other biological particle detection are discussed.
First FDA Approval of Dual Anti-HER2 Regimen: Pertuzumab in Combination with Trastuzumab and Docetaxel for HER2-Positive Metastatic Breast Cancer (2013)

On June 8, 2012, the U.S. Food and Drug Administration (FDA) approved pertuzumab (Perjeta, Genentech) for use in combination with trastuzumab (Herceptin, Genentech) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 808 patients with HER2-positive MBC. Patients were randomized (1:1) to receive pertuzumab (n = 402) or placebo (n = 406) in combination with trastuzumab and docetaxel. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). A statistically significant improvement in PFS (difference in medians of 6.1 months) was observed in patients receiving pertuzumab [HR, 0.62; 95% confidence interval (CI), 0.51-0.75; P < 0.0001]. A planned interim analysis suggested an improvement in OS (HR, 0.64; 95% CI, 0.47-0.88; P = 0.0053) but the HR and P value did not cross the stopping boundary. Common adverse reactions (>30%) observed in patients on the pertuzumab arm included diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. No additive cardiac toxicity was observed. Significant manufacturing issues were identified during the review. On the basis of substantial evidence of efficacy for pertuzumab in MBC and the compelling public health need, FDA did not delay availability to patients pending final resolution of all manufacturing concerns. Therefore, FDA approved pertuzumab but limited its approval to lots not affected by manufacturing problems. The applicant agreed to multiple manufacturing and testing postmarketing commitments under third-party oversight to resolve manufacturing issues.
Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. (1984)

A soluble enzyme preparation from immature sage (Salvia officinalis) leaves has been shown to catalyze the cation-dependent cyclization of geranyl pyrophosphate to the isomeric monoterpene olefins (+/-)-alpha-pinene and (-)-beta-pinene and to lesser amounts of camphene and limonene (Gambliel, H., and Croteau, R. (1982) J. Biol. Chem. 257, 2335-2342). This preparation was fractionated by gel filtration on Sephadex G-150 to afford two regions of enzymic activity termed geranyl pyrophosphate:pinene cyclase I (Mr approximately equal to 96,000), which catalyzed the conversion of geranyl pyrophosphate to the bicyclic olefin (+)-alpha-pinene, and to smaller quantities of the rearranged olefin (+)-camphene and the monocyclic olefin (+)-limonene, and geranyl pyrophosphate:pinene cyclase II (Mr approximately equal to 55,000), which transformed the acyclic precursor to (-)-alpha-pinene and (-)-beta-pinene, as well as to (-)-camphene, (-)-limonene, and the acyclic olefin myrcene. The multiple olefin biosynthetic activities co-purified with pinene cyclase I on four subsequent chromatographic and electrophoretic steps, and the ability to cyclize geranyl pyrophosphate and the related allylic pyrophosphates neryl pyrophosphate and linalyl pyrophosphate was likewise coincident throughout purification. Fractionation of pinene cyclase II by an identical sequence showed that the activities for the synthesis of the stereochemically related (-)-olefins co-purified, as did the ability to utilize the three acyclic precursors. The general properties of cyclase I and cyclase II were determined, and a scheme for the biosynthesis of the pinenes and related monoterpene olefins was proposed.
Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics (2013)

During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.
Augmentation of metalloproteinase (gelatinase) activity secreted from Rous sarcoma virus-infected cells correlates with transforming activity of src. (1995)

To search for the biochemical properties of cells relevant to transformation by p60v-src, we examined the activities and amounts of metalloproteinase (gelatinase) released from chicken embryonic fibroblasts infected with various mutants of Rous sarcoma virus by zymography and immunoblotting. While nontransforming Src proteins, including cellular p60c-src and its nonmyristylated form, had no stimulatory effect, wild-type p60v-src and the transforming mutant of cellular p60c-src stimulated the secretion and proteolytic activation of metalloproteinases. Moreover, the activation of metalloproteinase secretion strongly correlated with the invasiveness of cells assayed by the modified Boyden Chamber method. Chimeric mutants between v-src and c-src, which are transforming but produce less distinct morphological changes in infected cells, also stimulated the secretion of metalloproteinases as well as wild-type p60v-src. Deletion mutants of v-Src in which varying portions of the NH2-terminal half of p60v-src are deleted stimulated secretion to a level similar to that of wild-type regardless of the degree of morphological change they induce. Together with Src protein, other oncogene products including Yes, Fps, ErbB and Crk were also found to stimulate the secretion of metalloproteinases. Thus, these results suggest that transformation of cells with src and other oncogenes is closely associated with the enhanced secretion of metalloproteinases that may play an important role in tumor invasion and metastasis.
DYNAMIC CONSTRAINED DELAUNEY TRIANGULATION AND APPLICATION TO MULTICHIP MODULE LAYOUT (M.S. Thesis) (1991)

The *Voronoi diagram* is a partition of a set S of N points in a plane, such that each region is the locus of the points (x, y) closer to a point of S than to any other point of S. If no four points are co-circular, the *Delaunay triangulation* is the straight-line dual of the Voronoi diagram. The triangulation may be *constrained*, that is, a set of straight-line segments may be prespecified. This thesis presents some characteristics of constrained Delaunay triangulation and introduces a set of numerically stable algorithms for incremently constructing and updating constrained Delaunay triangulation. The dynamic constrained Delaunay triangulation algorithms have been implemented in a layout system for multichip modules. It has been used as the underlying data representation for rubber-band sketch, a topological routing for one layer. We have proved the O(n log n) expected running time for the Delauney triangulation algorithm.
Palmitylation of an amino-terminal cysteine motif of protein tyrosine kinases p56lck and p59fyn mediates interaction with glycosyl-phosphatidylinositol-anchored proteins. (1993)

Cross-linking of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins on T cells can trigger cell activation. We and others have shown an association between GPI-anchored proteins and the protein tyrosine kinases (PTKs) p56lck and p59fyn, suggesting a pathway for signaling through GPI-anchored proteins. Studies of decay-accelerating factor (DAF) or CD59 in either the C32 cell line or the HeLa cell line transfected with PTK cDNA demonstrated that the GPI-anchored proteins associated noncovalently with p56lck and p59fyn but not with p60src. Nonmyristylated versions of p56lck and p59fyn also failed to associate with the GPI-anchored proteins. Mutational analysis of the PTK demonstrated that the association with the GPI-anchored proteins mapped to the unique amino-terminal domains of the PTK. A chimeric PTK consisting of the 10 amino-terminal residues of p56lck or p59fyn replacing the corresponding amino acids in p60src was sufficient for association with DAF, but the converse constructs containing the first 10 amino acids of p60src plus the remainder of p56lck or p59fyn did not associate with DAF. Mutation of cysteine to serine at positions 3 and 6 in p59fyn or positions 3 and 5 in p56lck abolished the association of these kinases with DAF. Mutation of serine to cysteine at positions 3 and 6 in p60src conferred on p60src the ability to associate with DAF. Direct labeling with [3H]palmitate demonstrated palmitylation of this amino-terminal cysteine motif in p56lck. Thus, palmitylation of the amino-terminal cysteine residue(s) together with myristylation of the amino-terminal glycine residue defines important motifs for the association of PTKs with GPI-anchored proteins.
Symptomatic Gastroesophageal Reflux as a Risk Factor for Esophageal Adenocarcinoma (1999)

There is a strong and probably causal relation between gastroesophageal reflux and esophageal adenocarcinoma. The relation between reflux and adenocarcinoma of the gastric cardia is relatively weak.
Continuous propionate production from whey permeate using a novel fibrous bed bioreactor (1994)

Continuous production of propionate from whey lactose by Propionibacterium acidipropionici immobilized in a novel fibrous bed bioreactor was studied. In conventional batch propionic acid fermentation, whey permeate without nutrient supplementation was unable to support cell growth and failed to give satisfactory fermentation results for over 7 days. However, with the fibrous bed bioreactor, a high fermentation rate and high conversion were obtained with plain whey permeate and de-lactose whey permeate. About 2% (wt/vol) propionic acid was obtained from a 4.2% lactose feed at a retention time of 35 to 45 h. The propionic acid yield was approximately 46% (wt/vol) from lactose. The optimal pH for fementation was 6.5, and lower fermentation rates and yields were obtained at lower pH values. The optimal temperature was 30 degrees C, but the temperature effect was not dramatic in the range of 25 to 35 degrees C. Addition of yeast extract and trypticase to whey permeate hastened reactor startup and increased the fermentation rate and product yields, but the addition was not required for long-term reactor performance. The improved fermentation results with the immobilized cell bioreactor can be attributed to the high cell density, approximately 50 g/L, attained in the bioreactor, Cells were immobilized by loose attachement to fiber surfaces and entrapment in the void spaces within the fibrous matrix, thus allowing constant renewal of cells. Consequently, this bioreactor was able to operate continuously for 6 months without encountering any clogging, degeneration, or contamination problems. Compared to conventional batch fermentors, the new bioreactor offers many advantages for industrial fermentation, including a more than 10-fold increase in productivity, acceptance of low-nutrient feedstocks such as whey permeate, and resistance to contamination. (c) 1994 John Wiley & Sons, Inc.
Discussion of “The Evaluation of Forensic DNA Evidence” (1997)

The current study began in 1994 as an update to the 1992 report on the issues of (i) the accuracy of laboratory determinations and (ii) the accuracy of calculations based on population and genetics theory and the available databases and the statistical assessments of similarities …
Interpolation by the FFT revisited-an experimental investigation (1989)

A numerical investigation into the accuracy of interpolation by, fast Fourier transform (FFT), using a sinusoidal test signal, is described. The method is precisely defined, including a previously unnoticed detail which makes a significant difference to the accuracy of the result. The experiments show that, with no input windowing, the accuracy of interpolation is almost independent of sinusoidal wavelength very close to the Nyquist limit. The resulting RMS error is inversely proportional to input sequence length and is very low for sequence lengths likely to be encountered in practice. As wavelength passes through the Nyquist limit, there is a sudden increase in error, as is expected from sampling theory. If the sequence ends are windowed by short, cosine half-bells, accuracy is further improved at longer wavelengths. In comparison, small-kernal convolution methods, such as linear interpolation and cubic convolution, perform badly at wavelengths anywhere near the Nyquist limit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhanced hole mobilities in surface-channel strained-Si p-MOSFETs (2002)

The strain dependence of the hole mobility in surface-channel p-MOSFETs employing pseudomorphic, strained-Si layers is reported for the first time. The hole mobility enhancement is observed to increase roughly linearly with the strain as the Ge content in the relaxed Si/sub 1-x/Ge/sub x/ buffer layer increases. When compared to the device with x=0.1, the devices with x=0.22 and 0.29 exhibit hole mobility enhancement factors of 1.4 and 1.8, respectively. In spite of the high fixed charge in our gate oxides, the device with Ge content x=0.29 still exhibits a mobility 1.3 times that of bulk Si MOSFETs with state-of-the-art oxides. The first measurements of the transconductance enhancements in submicron strained-Si p-MOSFETs are also reported.