gebhart/patrepeval huggingface dataset:
Fiber-Amplifier Cascades with Equalization Employing Mach-Zehnder Optical Filters in Multiwavelength Systems (1994)

Recent rapid advances in Erbium-Doped Fiber Amplifier (EDFA) technology make the WDM option particularly attractive for increased capacity and multiple access optical networking [1-2], In these applications, cascaded EDFAs may be deployed on a large scale in future lightwave systems. However, the nonflat gain spectra of the EDFAs impose a difficulty in optical networks using WDM technology since each optical channel experiences a different optical gain. Although each individual amplifier exhibits only modest gain variations over a spectral interval of roughly 20 nm, these variations accumulate through successive amplifiers, resulting in exponentially increasing interchannel power differences [3]. Various proposals for equalizers have been discussed.
Similarity Metric Learning for a Variable-Kernel Classifier (1995)

Nearest-neighbor interpolation algorithms have many useful properties for applications to learning, but they often exhibit poor generalization. In this paper, it is shown that much better generalization can be obtained by using a variable interpolation kernel in combination with conjugate gradient optimization of the similarity metric and kernel size. The resulting method is called variable-kernel similarity metric (VSM) learning. It has been tested on several standard classification data sets, and on these problems it shows better generalization than backpropagation and most other learning methods. The number of parameters that must be determined through optimization are orders of magnitude less than for backpropagation or radial basis function (RBF) networks, which may indicate that the method better captures the essential degrees of variation in learning. Other features of VSM learning are discussed that make it relevant to models for biological learning in the brain.
Activated H-ras Rescues E1A-Induced Apoptosis and Cooperates with E1A To Overcome p53-Dependent Growth Arrest (1995)

The adenovirus E1A oncogene products stimulate DNA synthesis and cell proliferation but fail to transform primary baby rat kidney (BRK) cells because of the induction of p53-mediated programmed cell death (apoptosis). Overexpression of dominant mutant p53 (to abrogate wild-type p53 function) or introduction of apoptosis inhibitors, such as adenovirus E1B 19K or Bcl-2 oncoproteins, prevents E1A-induced apoptosis and permits transformation of BRK cells. The ability of activated Harvey-ras (H-ras) to cooperate with E1A to transform BRK cells suggests that H-ras is capable of overcoming the E1A-induced, p53-dependent apoptosis. We demonstrate here that activated H-ras was capable of suppressing apoptosis induced by E1A and wild-type p53. However, unlike Bcl-2 and the E1B 19K proteins, which completely block apoptosis but not p53-dependent growth arrest, H-ras expression permitted DNA synthesis and cell proliferation in the presence of high levels of wild-type p53. The mechanism by which H-ras regulates apoptosis and cell cycle progression is thereby strikingly different from that of the E1B 19K and Bcl-2 proteins. BRK cells transformed with H-ras and the temperature sensitive murine mutant p53(val 135), which lack E1A, underwent growth arrest at the permissive temperature for wild-type p53. p53-dependent growth arrest, however, could be relieved by E1A expression. Thus, H-ras alone was insufficient and cooperation of H-ras and E1A was required to override growth suppression by p53. Our data further suggest that two complementary growth signals from E1A plus H-ras can rescue cell death and thus permit transformation.
Induction of T cell activation by monoclonal antibodies specific for the transferrin receptor (1990)

The effect of the monoclonal antibodies (mAb), FG 1/5, FG 1/6 and FG 2/12, specific for different epitopes of the transferrin receptor (TfR) on T cell activation was studied. mAb FG 1/6 but not FG 2/12 or FG 1/5 was able to induce T cell proliferation in presence of submitogenic doses of phorbol esters. The costimulatory effect of FG 1/6 was seen only with phorbol esters known to be activators of protein kinase C. This proliferation occurred at low concentration (0.5 micrograms/ml) of antibody, required the simultaneous presence of both stimuli, phorbol esters and FG 1/6, and was independent of the presence of accessory cells. Furthermore, FG 1/6 mAb was able to increase the rate of modulation of CD3 surface expression induced by phorbol esters. FG 1/6 induced interleukin (IL) 2 synthesis by normal and transformed T lymphocytes. In addition, anti-IL2 receptor antibodies inhibited FG 1/6 plus phorbol ester-induced proliferation. Our results indicate that FG 1/6 mAb may provide to the T cells complementary signals to protein kinase C and that this activation is mediated by the IL2/IL 2R pathway.
Amide I modes in the N-methylacetamide dimer and glycine dipeptide analog: Diagonal force constants (2003)

The local amide I mode frequency of a peptide has been found to be strongly affected by the interpeptide interaction, because the electronic and molecular structures of the peptide bond change due to the electrostatic interaction with surrounding peptides. Ab initio vibrational analyses of three different series of N-methylacetamide dimers and glycine dipeptide analog in α-helical and β-sheet conformations have been performed. It is found that the diagonal force constant shift originates from the electronic structure change of a given peptide in combination with the cubic anharmonicity of the local amide I mode.
Rituximab in B-Cell chronic lymphocytic leukemia (2003)

The monoclonal anti-CD20 antibody rituximab exerts its antitumor activity through a variety of mechanisms, including acting against the cellular defects in apoptosis that give rise to B-chronic lymphocytic leukemia (B-CLL). Phase II clinical studies demonstrated that rituximab, given weekly as a single agent, exhibits significantly less activity in B-CLL than in indolent B-cell lymphomas. Dose escalation, achieved by a thrice-weekly dosing schedule, is necessary for rituximab to effect significant clinical activity as a single agent. A multicenter, prospective, randomized trial demonstrated that concurrent administration with fludarabine improves the complete response (CR) rate. Ongoing clinical studies are examining the use of rituximab in other combination regimens, including FCR (fludarabine, cyclophosphamide, and rituximab), which has shown great promise in a single-center phase II trial. B-CLL patients may experience more infusion toxicity, including tumor lysis syndrome, to rituximab than patients with lymphoma. However, such infusion toxicity is minimized with appropriate premedication and a stepped up dosing schedule, allowing safe and effective use of rituximab in this disease.
Captopril-Induced Functional Renal Insufficiency in Patients with Bilateral Renal-Artery Stenoses or Renal-Artery Stenosis in a Solitary Kidney (1983)

Medical Intelligence from The New England Journal of Medicine — Captopril-Induced Functional Renal Insufficiency in Patients with Bilateral Renal-Artery Stenoses or Renal-Artery Stenosis in a Solitary Kidney
Cellular and Molecular Surrogate Markers to Monitor Targeted and Non- Targeted Antiangiogenic Drug Activity and Determine Optimal Biologic Dose (2005)

Perhaps the most significant recent advance in oncology therapeutics has been the approval of various "molecularly targeted" anti-cancer drugs. Currently, there are a large number of similar drugs in early or late stage development, including antiangiogenic agents. Clinical development of such drugs suffers from several handicaps including determining whether a patient's cancer expresses the target and is functionally contributing to cancer growth, monitoring biologic activity, and determining optimal biologic dose. The last problem is related to the low frequency of objective tumor responses (tumor shrinkage) caused by such drugs, or the lack of dose limiting toxicities necessary to define a maximum tolerated dose (MTD), or expression of optimal therapeutic activity at doses below the MTD, when one can be defined. These problems necessitate the development of alternative pharmacodynamic surrogate markers. Here we summarize several such promising markers for monitoring targeted antiangiogenic activity, and establishing optimal therapeutic/biologic dosing. The first is molecular--plasma VEGF--levels of which are rapidly and significantly increased in a dose dependent manner after injection of normal or tumor bearing mice with anti-VEGFR-2 antibodies. The second is a cellular marker, and more generic in nature--circulating VEGF receptor-2 positive cells found in peripheral blood, some of which may be circulating endothelial progenitor cells. Levels of such cells are suppressed in a dose dependent manner which correlate with previously determined optimal biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or treatments. Finally, another promising marker we discuss is soluble VEGFR-2.
Omega-3 Fatty Acids Supplementation Restores Mechanisms that Maintain Brain Homeostasis in Traumatic Brain Injury (2007)

Traumatic brain injury (TBI) produces a state of vulnerability that reduces the brain capacity to cope with secondary insults. The silent information regulator 2 (Sir2) has been implicated with maintaining genomic stability and cellular homeostasis under challenging situation. Here we explore the possibility that the action of Sir2alpha (mammalian Sir2) in the brain can extend to serve neuronal plasticity. We provide novel evidence showing that mild TBI reduces the expression of Sir2alpha in the hippocampus, in proportion to increased levels of protein oxidation. In addition, we show that dietary supplementation of omega-3 fatty acids that ameliorates protein oxidation was effective to reverse the reduction of Sir2alpha level in injured rats. Given that oxidative stress is a subproduct of dysfunctional energy homeostasis, we measured AMP-activated protein kinase (AMPK) and phosphorylated-AMPK (p-AMPK) to have an indication of the energy status of cells. Hippocampal levels of total and phosphorylated AMPK were reduced after TBI and levels were normalized by omega-3 fatty acts supplements. Further, we found that TBI reduced ubiquitous mitochondrial creatine kinase (uMtCK), an enzyme implicated in the energetic regulation of Ca2+-pumps and in the maintenance of Ca2+-homeostasis. Omega-3 fatty acids supplements normalized the levels of uMtCK after lesion. Furthermore, we found that the correlation between Sir2alpha and AMPK or p-AMPK was disrupted by TBI, but restored by omega-3 fatty acids supplements. Our results suggest that TBI may compromise neuronal protective mechanisms by involving the action of Sir2alpha. In addition, results show the capacity of omega-3 fatty acids to counteract some of the effects of TBI by normalizing levels of molecular systems associated with energy homeostasis.
A PCR-based method for high stringency screening of DNA libraries (1993)

A rapid method for cloning genomic DNA utilizing a PCR-based screening protocol is described. A murine genomic library in lambda phage was subdivided into 64 wells, each containing 1000 clones, and propagated in bacteria. Amplified phage from each of 8 wells across columns, and each of 8 wells down rows, were pooled. The pooled phage were screened for the presence of murine M-CSF DNA by PCR using specific oligonucleotide primers. A single well that contained an M-CSF genomic clone was identified by the synthesis of a PCR product of the correct size that hybridized to an internal M-CSF oligonucleotide probe. This well was subdivided into 64 wells, each containing approximately 30 individual phage, reamplified, and rescreened utilizing the same protocol. A positive well was then subdivided and amplified a third time starting with an average of 2 phage per well, and rescreened for M-CSF DNA by PCR. Phage from a PCR-positive well, now highly enriched for M-CSF DNA, were grown as individual plaques. PCR-screening of randomly picked plaques demonstrated that the majority contained an M-CSF genomic insert. This method obviates the more labor and time intensive method of plaque hybridization screening of DNA libraries, and is more stringent since three oligonucleotides (the two PCR primers, and the hybridization probe) are required to give a true positive signal. Similar methodology has also been used to clone a cDNA gene contained within a plasmid library.
Polycaprolactone and Bovine Serum Albumin Based Nanofibers for Controlled Release of Nerve Growth Factor (2009)

Tissue engineering approaches for peripheral nerve regeneration employ biodegradable scaffolds coupled with growth factors for improved performance in regeneration of large nerve injuries. Electrospun nanofibers provide a versatile platform for fabrication of scaffolds with extracellular matrix like architecture and increased surface area. Incorporation of growth factors in nanofibers have been previously demonstrated using oil in water emulsion techniques but are associated with burst release and loss of valuable growth factor. Here, we show a novel blend of polycaprolactone and bovine serum albumin (BSA) to form nanofibers containing nerve growth factors. The BSA helps in overcoming the most common drawbacks associated with hydrophobic polymers such as reduced loading efficiency, long degradation periods, and burst release. The controlled release of nerve growth factor (NGF) from the nanofibers was evaluated using enzyme linked immune sorbent assay (ELISA) and PC12 based bioassay over a 28 day time period. A sustained release of NGF was obtained for at least 28 days. PC12 bioassays confirmed the bioactivity of the NGF, and showed that the released NGF was sufficient to induce neurite outgrowth from PC12 cells throughout the period of release, therefore, demonstrating the successful incorporation and controlled release potential of PCL BSA scaffolds.
Signaling by the CD19/CD21 Complex on B Cells (2003)

Early studies, largely based on in vitro models, revealed potential functional roles for the components of the CD19/21/81 complex in B cell proliferation and antibody production. These studies also identified signal transduction pathways linked to these receptors. Over the last decade, studies on knockout mice defined the biologic functions of CD19, CD21 and CD81. This review focuses on current attempts to use these receptors as tools to understand how the immune system regulates responsiveness and tolerance, while correlating specific biochemical pathways with biologic function.
Map of distamycin, netropsin, and actinomycin binding sites on heterogeneous DNA: DNA cleavage-inhibition patterns with methidiumpropyl-EDTA.Fe(II). (1982)

We report a direct technique for determining the binding sites of small molecules on naturally occurring heterogeneous DNA. Methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II) cleaves double helical DNA with low sequence specificity. Using a combination of MPE.Fe(II) cleavage of drug-protected DNA fragments and Maxam-Gilbert gel methods of sequence analysis, we have determined the preferred binding sites on a Rsa I-EcoRI restriction fragment from pBR322 for the intercalator actinomycin D and the minor groove binders netropsin and distamycin A. Netropsin and distamycin A gave identical DNA cleavage-inhibition patterns and bound preferentially to A+T-rich regions with a minimal protected site of four base pairs. We were able to observe the effect of increasing concentration on site selection by netropsin and distamycin A. Actinomycin D afforded a completely different cleavage-inhibition pattern, with 4- to 16-base-pair-long protected regions centered around one or more G.C base pairs.
Superpulse CO2 laser treatment of facial syringomata (1987)

Eight patients with facial syringomata have been treated with the superpulse CO2 laser and followed for periods up to 3 years. Superpulse capability allows satisfactory photovaporization of overlying skin and exposure and liberation of the underlying cyst. Healing was satisfactory with minimal scarring and no persistence or recurrence of syringomata in five of eight cases.
Induction of persistent T cell hyporesponsiveness in vivo by monoclonal antibody to ICAM-1 in patients with rheumatoid arthritis. (1995)

Rheumatoid arthritis patients undergoing treatment with a murine mAb (BIRR1) to ICAM-1 were studied to determine the effects of the treatment on T cell responsiveness assayed in vitro. Previous studies had demonstrated that over the 5-day treatment period, there was a transient increase in circulating T cells that returned to base line 3 days after therapy. The transient lymphocytosis correlated with a loss in delayed-type hypersensitivity reactivity during the time of Ab administration. However, neither the increase in T cell numbers nor the inhibition of delayed-type hypersensitivity responses correlated with the immediate clinical benefit of therapy or the prolonged nature of the response to therapy in some patients. The current studies show that after the return of lymphocyte numbers to pretreatment levels, a decrease in T lymphocyte responses to suboptimal activation signals, including accessory cell-dependent (low dose PHA and soluble anti-CD3 mAb) and accessory cell-independent stimuli (immobilized anti-CD3 mAb), was observed. However, responses to recall Ags were preserved. Depressed T cell responses were not the result of diminished accessory cell function or production of suppressive factors by monocytes, but rather reflected decreased IL-2 production. The duration of T cell hyporesponsiveness was variable in length but lasted up to 5 mo after treatment with anti-ICAM-1 mAb. The induction and persistence of T cell hyporesponsiveness correlated with an improvement in disease activity in treated patients. These studies show that treatment with anti-ICAM-1 mAb can induce T cell hyporesponsiveness that correlates with and may explain sustained therapeutic benefit in patients with rheumatoid arthritis.
Structural and Genetic Analysis of Electrostatic and Other Interactions in Bacteriophage T4 Lysozyme (2007)

The lysozyme from bacteriophage T4 is being used as a model system to determine the roles of individual amino acids in the folding and stability of a typical globular protein. Such studies can provide quantitative information on the contributions made by different types of interactions including hydrogen bonds, hydrophobic interactions, salt bridges and disulphide bridges. To determine the contribution of long-range electrostatic interactions a combination of charge-change mutations was used to reduce the overall formal charge on T4 lysozyme at neutral pH from +9 to +1 units. Such changes in charge were found to have little effect on the stability of the molecule. Salt bridges engineered on the surface of the protein also were found to contribute little to stability. In contrast, the introduction of acidic groups designed to interact with the partial positive charges at the N-termini of alpha-helices consistently increased the stability of the protein. It is argued that this difference between electrostatic salt-bridge interactions and electrostatic 'helix-dipole' interactions lies in the entropic cost of bringing together the interacting partners. In an attempt to simplify the folding problem, and also to further investigate the helix propensity of different amino acids, a series of alanines was introduced within an alpha-helix of T4 lysozyme. The resultant protein not only folds normally but is also more stable than the wild-type enzyme, adding further support to recent evidence that alanine is a helix-favouring amino acid.
LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli (2002)

Summary The function of the LysR‐type regulator LrhA of Escherichia coli was defined by comparing whole‐genome mRNA profiles from wild‐type E. coli and an isogenic lrhA mutant on a DNA microarray. In the lrhA mutant, a large number (48) of genes involved in flagellation, motility and chemotaxis showed relative mRNA abundances increased by factors between 3 and 80. When a representative set of five flagellar, motility and chemotaxis genes was tested in lacZ reporter gene fusions, similar factors for derepression were found in the lrhA mutant. In gel retardation experiments, the LrhA protein bound specifically to flhD and lrhA promoter DNA (apparent K D ≈ 20 nM), whereas the promoters of fliC , fliA and trg were not bound by LrhA. The expression of flhDC (encoding FlhD 2 C 2 ) was derepressed by a factor of 3.5 in the lrhA mutant. FlhD 2 C 2 is known as the master regulator for the expression of flagellar and chemotaxis genes. By DNase I footprinting, LrhA binding sites at the flhDC and lrhA promoters were identified. The lrhA gene was under positive autoregulation by LrhA as shown by gel retardation and lrhA expression studies. It is suggested that LrhA is a key regulator controlling the transcription of flagellar, motility and chemotaxis genes by regulating the synthesis and concentration of FlhD 2 C 2 .
Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome (2008)

Mutations in the X-linked MECP2 gene cause Rett syndrome, a neurodevelopmental disorder that exclusively affects girls. Females with the MECP2 mutations exhibit a broad spectrum of clinical presentations ranging from classical Rett syndrome to asymptomatic carriers, which can be explained by differences in X chromosome inactivation (XCI). Here, we report a family with a girl with Rett syndrome in whom a novel missense mutation in the MECP2 gene was transmitted through the maternal germ line. The carrier mother was asymptomatic and presented non-random XCI in the peripheral blood cells, which resulted in the X chromosome harboring the mutant allele that was predominantly active. Thus, the presence of non-random XCI in the peripheral blood cells did not provide an explanation for the normal phenotype of the carrier mother. This result suggests that mechanisms other than XCI may contribute to the phenotypic heterogeneity associated with MECP2 mutations.
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis (2006)

In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contains megakaryocyte potential. Combining progenitor assays with immunohistochemical analysis, we identified 2 waves of MEPs in the yolk sac associated with the primitive and definitive erythroid lineages. Primitive MEPs emerge at E7.25 along with megakaryocyte and primitive erythroid progenitors, indicating that primitive hematopoiesis is bilineage in nature. Subsequently, definitive MEPs expand in the yolk sac with Meg-CFCs and definitive erythroid progenitors. The first GP1bbeta-positive cells in the conceptus were identified in the yolk sac at E9.5, while large, highly reticulated platelets were detected in the embryonic bloodstream beginning at E10.5. At this time, the number of megakaryocyte progenitors begins to decline in the yolk sac and expand in the fetal liver. We conclude that the megakaryocyte lineage initially originates from hemangioblast precursors during early gastrulation and is closely associated both with primitive and with definitive erythroid lineages in the yolk sac prior to the transition of hematopoiesis to intraembryonic sites.