gebhart/patrepeval huggingface dataset:
A Learning Algorithm for Boltzmann Machines* (1985)

The computational power of massively parallel networks of simple processing elements resides in the communication bandwidth provided by the hardware connections between elements. These connections can allow a significant fraction of the knowledge of the system to be applied to an instance of a problem in a very short time. One kind of computation for which massively parallel networks appear to be well suited is large constraint satisfaction searches, but to use the connections efficiently two conditions must be met: First, a search technique that is suitable for parallel networks must be found. Second, there must be some way of choosing internal representations which allow the preexisting hardware connections to be used efficiently for encoding the constraints in the domain being searched. We describe a general parallel search method, based on statistical mechanics, and we show how it leads to a general learning rule for modifying the connection strengths so as to incorporate knowledge about a task domain in an efficient way. We describe some simple examples in which the learning algorithm creates internal representations that are demonstrably the most efficient way of using the preexisting connectivity structure.
Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery (2008)

Drug delivery, magnetic resonance and fluorescence imaging, magnetic manipulation, and cell targeting are simultaneously possible using a multifunctional mesoporous silica nanoparticle. Superparamagnetic iron oxide nanocrystals were encapsulated inside mesostructured silica spheres that were labeled with fluorescent dye molecules and coated with hydrophilic groups to prevent aggregation. Water-insoluble anticancer drugs were delivered into human cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to that in non-cancerous fibroblasts. The highly versatile multifunctional nanoparticles could potentially be used for simultaneous imaging and therapeutic applications.
Pan-cancer patterns of somatic copy number alteration (2013)

Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs.
Adult Neurogenesis: From Precursors to Network and Physiology (2005)

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.
Effects of Blood-Processing Protocols on Fetal and Total DNA Quantification in Maternal Plasma (2001)

Standardization in plasma-processing protocols is needed for maternal plasma DNA analysis, especially for quantification of total DNA in maternal plasma. Such preanalytic factors may also affect other applications of plasma DNA analysis.
Review of Dimethyl Carbonate (DMC) Manufacture and Its Characteristics as a Fuel Additive (1997)

Dimethyl carbonate (DMC) is considered an option for meeting the oxygenate specifications on gasoline and as a means of converting natural gas to a liquid transportation fuel. In this report, the fuel characteristics and known chemical synthesis schemes for DMC are reviewed. Three production schemes have a commercial track record, while others are still under development. The older of the three commercially proven schemes is undesirable because it employs phosgene. The other two commercially proven schemes have a complex mixture of advantages and disadvantages with regard to the synthesis chemistry and are reviewed in greater detail. One other commercially viable production scheme that involves coproduction of either ethylene or propylene glycol is also reviewed. This scheme is still in the development stage and would require a commitment to coproduce the glycol from ethylene or propylene. The authors are not aware of any refiner that either has blended or is blending DMC into gasoline for commercial use.
Nerve growth factors (1989)

Part 1 Purification: purification of nerve growth factor, F.M.Longo et al ciliary neurotrophic factors, M.Manthorpe et al neuroleukin, M.E.Gurney. Part 2 Bioassay: use of collagen gels to bioassay nerve growth factor activity, T.E.Ebendal neurotrophic factor biossay using dissociated neurons, A.M.Davies CNS neurons, J.E.Johnson the quantitative bioassay of nerve growth factor with PC12 cells, L.A.Greene and A.Rukenstein chromaffin cell cultures and their use for assaying effects of nerve growth factor and other growth factors, K.Unsicker et al. Part 3 Histology: histological identification of nerve growth factor and its mRNA, R.A.Rush et al. Part 4 Administration: in vivo administration of nerve growth factor, I.A.Hendry antibodies to nerve growth factor as a neurotoxin and biological probe, E.M.Johnson and I.A.Ferguson. Part 5 Analysis and assay of mRNA NGF: analysis of a transcription unit, M.J.Selby et al quantitative measurement of nerve growth factor mRNA, D.O.Clegg et al. Part 6 Receptors: purification of the nerve growth factor receptor, M.Blaber et al characterization of NGF receptors, M.Bothwell quantitative radioautography for NGF receptors, P.M.Richardson et al NGF receptor expression - molecular approaches, C.R.Buck and M.V.Chao.
Designing, fabricating, and imaging Raman hot spots (2006)

We have developed a probe of the electromagnetic mechanism of surface-enhanced Raman scattering via Au nanodisk arrays generated by using on-wire lithography. In this approach, disk thickness and interparticle gap are precisely controlled from 5 nm to many micrometers. Confocal Raman microscopy demonstrates that disk thickness and gap play a crucial role in determining surface-enhanced Raman scattering intensities. Theoretical calculations also demonstrate that these results are consistent with the electromagnetic mechanism, including the surprising result that the largest enhancement does not occur for the smallest gaps.
Real-Time US versus CT Determination of Pubic Arch Interference for Brachytherapy (2001)

Transrectal US PAI determination is easily performed, intraoperatively useful, and accurate. CT can result in PAI overestimation. Reducing direct CT costs and the indirect costs of unnecessary hormonal therapy for false-positive PAI will reduce expense and improve patient care. Transrectal US should replace CT for PAI determination.
Regulation of fibrinogen assembly. Transfection of Hep G2 cells with B beta cDNA specifically enhances synthesis of the three component chains of fibrinogen. (1990)

Previous studies indicated that synthesis of B beta chain may be a rate-limiting factor in the production of human fibrinogen since Hep G2 cells contain surplus pools of A alpha and gamma but not of B beta chains, and fibrinogen assembly commences by the addition of preformed A alpha and gamma chains to nascent B beta chains attached to polysomes. To test whether B beta chain synthesis is rate limiting Hep G2 cells were transfected with B beta cDNA, and its effect on fibrinogen synthesis and secretion was measured. Two sets of stable B beta cDNA-transfected Hep G2 cells were prepared, and both cell lines synthesized 3-fold more B beta chains than control cells. The B beta-transfected cells also synthesized and secreted increased amounts of fibrinogen. Transfection with B beta cDNA not only increased the synthesis of B beta chain but also increased the rate of synthesis of the other two component chains of fibrinogen and maintained surplus intracellular pools of A alpha and gamma chains. Transfection with B beta cDNA did not affect the synthesis of albumin, transferrin, or anti-chymotrypsin and had a small inhibitory effect on the synthesis of C-reactive protein. Taken together these studies demonstrate that increased B beta chain synthesis specifically causes increased production of the other two component chains of fibrinogen and that unequal and surplus amounts of A alpha and gamma chains are maintained intracellularly.
Striking a balance: Modulation of the actin cytoskeleton bySalmonella (2000)

Salmonella spp. have evolved the ability to enter into cells that are normally nonphagocytic. The internalization process is the result of a remarkable interaction between the bacteria and the host cells. Immediately on contact, Salmonella delivers a number of bacterial effector proteins into the host cell cytosol through the function of a specialized organelle termed the type III secretion system. Initially, two of the delivered proteins, SopE and SopB, stimulate the small GTP-binding proteins Cdc42 and Rac. SopE is an exchange factor for these GTPases, and SopB is an inositol polyphosphate phosphatase. Stimulation of Cdc42 and Rac leads to marked actin cytoskeleton rearrangements, which are further enhanced by SipA, a Salmonella protein also delivered into the host cell by the type III secretion system. SipA lowers the critical concentration of G-actin, stabilizes F-actin at the site of bacterial entry, and increases the bundling activity of the host-cell protein T-plastin (fimbrin). The cellular responses stimulated by Salmonella are short-lived; therefore, immediately after bacterial entry, the cell regains its normal architecture. Remarkably, this process is mediated by SptP, another target of the type III secretion system. SptP exert its function by serving as a GTPase-activating protein for Cdc42 and Rac, turning these G proteins off after their stimulation by the bacterial effectors SopE and SopB. The balanced interaction of Salmonella with host cells constitutes a remarkable example of the sophisticated nature of a pathogen/host relationship shaped by evolution through a longstanding coexistence.
Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia (2015)

Targeted therapy has been the forefront of cancer treatment. Cancer immunotherapy is the most recent focus. In addition, novel immunotherapeutics targeting B cell receptor signaling (e.g., ibrutinib), T cell receptor ( e.g., CART19), and NK cells (e.g., AFM13) are being developed. This review summarized the new development in blinatumomab (MT103/MEDI-538), a first-in-class bispecific T engager (BiTE) antibody against CD19/CD3 in patients with relapsed/refractory precursor B cell acute lymphoid leukemia.
Convenient synthesis of substituted 3‐aminothiophene‐2‐carbonitriles from α‐acetylenic nitriles and their conversion to thieno[3,2‐d]pyrimidines (1986)

Abstract Several novel 2,4,6‐trisubstituted thieno[3,2‐ d ]pyrimidines were synthesized from the hitherto unknown 3‐amino‐5‐methyl‐(or 5‐phenyl)thiophene‐2‐carbonitriles 7 and 8 . o ‐Aminonitriles 7 and 8 were obtained in a single step by conjugate addition of mercaptoacetonitrile (generated in situ ) to substituted acetylenic nitriles 4 and 5 and annelation of the intermediate vinylic thioethers.
Nanofunctionalisation for the treatment of peripheral nervous system injuries (2006)

A construct based on the electrostatic layer-by-layer self assembly technique has been fabricated, to be used as a tailored device to encourage nerve regeneration. A multilayered nanocoating composed of three precursor bilayers of cationic poly(dimethyldiallylammonium) chloride (PDDA) and anionic poly(styrenesulfonate) (PSS), followed by bilayers of poly-D-lysine (PDL) and antibody specific to transforming growth factor 1 (anti-TGF-1), has been deposited on HYAFF 11. The assembly process has been monitored by quartz crystal microbalance (QCM) for its characterisation and then it has been used on HYAFF 11. Structural studies of the resulting multilayers confirmed stepwise deposition of anti-TGF-1, with an average layer thickness of 2.2+/-0.2 nm and an average surface density of 0.36+/-0.03 mug cm(-2). Scanning electron microscopy has been used to characterise multilayer uniformity. Finally, the immunological activity of the multilayered structure has been assessed. The results show that anti-TGF-1 can be included in its active form in a predetermined multilayered structure onto HYAFF 11 with quantitative control of layer thickness and weight, providing a high tool with great potential in tissue engineering.
Isolation, culture and characteristics of human foetal and adult retinal pigment epithelium (1998)

This mechanical dissection technique is recommended for the isolation of foetal and young adult RPE cells, while the enzyme digestion method is preferred for aged adult tissue.
Selective targeting of ITK blocks multiple steps of HIV replication (2008)

Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLCgamma-1, Ca(2+) mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
Specific Interaction of the Streptomyces Chitin‐Binding Protein Chb1 with α‐Chitin (1997)

Streptomyces olivaceoviridis secretes a so far unique protein of 18.7 kDa (CHB1) which lacks catalytic activity. It interacts highly specifically with α‐chitin, but not with β‐chitin, chitosan, or cellulose. Each of the five codons for tryptophan (Tip) in the chbl gene was replaced by those for leucine (Leu) or tyrosine (Tyr). Eight corresponding mutant proteins and the wild‐type protein were purified to homogeneity and their binding capacity to α‐chitin was determined. The relative affinities to anti‐CHB1 antibodies, the kinetics of binding, the dissociation constants, circular dichroism, and fluorescence emission spectra for three mutant types were compared to the characteristics of CHB1. The presented data lead to the following conclusions, (a) CHB1 presents a highly flexible protein lacking a‐helices. (b) Replacement of each of the buried Trp residues (Trpl34 and Trpl84) leads to conformational alterations and, in due course, to a considerably reduced binding affinity of the protein, (c) The exchange of the exposed Trp 57 by either Leu or Tyr results in relatively slight topological changes, but entails a loss of binding capacity of about 90%. (d) The dissociation constant was highest for the mutant protein [L57]CHB1 (2.17 μM), followed by [L134]CHB1 (0.91 μM) and [L184]CHB1 (0.26 μM), and lowest for the progenitor CHB1 (0.11 μM), indicating its strong affinity to the unsoluble substrate, (e) The data suggest that the exposed Trp57 contributes directly and significantly to the interaction of CHBl with α‐chitin.
Structure and Properties of Poly(vinyl alcohol)/Na+ Montmorillonite Nanocomposites (2000)

Poly(vinyl alcohol)/sodium montmorillonite nanocomposites of various compositions were created by casting from a polymer/silicate water suspension. The composite structure study revealed a coexistence of exfoliated and intercalated MMT layers, especially for low and moderate silicate loadings. The inorganic layers promote a new crystalline phase different than the one of the respective neat PVA, characterized by higher melting temperature and a different crystal structure. This new crystal phase reflects on the composite materials properties. Namely, the hybrid polymer/silicate systems have mechanical, thermal, and water vapor transmission properties, which are superior to that of the neat polymer and its conventionally filled composites. For example, for a 5 wt % MMT exfoliated composite, the softening temperature increases by 25 °C and the Young's modulus triples with a decrease of only 20% in toughness, whereas there is also a 60% reduction in the water permeability. Furthermore, due to the nanoscale dispersion of filler, the nanocomposites retain their optical clarity.
Identification of induction motor parameters from transient stator current measurements (1999)

This paper describes three methods for estimating the lumped model parameters of an induction motor using startup transient data. A three-phase balanced induction motor is assumed. Measurements of the stator currents and voltages are required for the identification procedure, but no measurements from the motor shaft are needed. The first method presented applies simple models with limited temporal domains of validity and obtains parameter estimates by extrapolating the model error bias to zero. This method does not minimize any specific error criterion and is presented as a means of finding a good initial guess for a conventional iterative maximum-likelihood or least-squares estimator. The second method presented minimizes equation errors in the induction motor model in the least-square sense using a Levenburg-Marquardt iteration. The third identification method is a continuation of the Levenburg-Marquardt method, motivated by observed properties of some pathological loss functions. The third method minimizes errors in the observations in the least-squared sense and is, therefore, a maximum-likelihood estimator under appropriate conditions of normality. The performance of the identification schemes is demonstrated with both simulated and measured data, and parameters obtained using the methods are compared with parameters obtained from standard tests.
The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes. (2002)

Fetal rat hepatocytes treated with transforming growth factor beta (TGF-beta) die by apoptosis. However, a subpopulation of them survives and undergoes an epithelial mesenchymal transition (EMT). This transition also occurs upon incubation with fetal bovine serum. We have isolated the subpopulations that undergo EMT (TGF-beta-treated-fetal hepatocytes: TbetaT-FH; serum-treated-fetal hepatocytes: ST-FH) and show that they present high levels of vimentin and Snail expression and lack cytokeratin 18 and E-cadherin. Both TbetaT-FH and ST-FH cells require mitogens to grow and maintain the response to TGF-beta in terms of growth inhibition. However, they lack differentiation markers such as the liver-enriched transcription factors hepatocyte nuclear factor 4 (HNF-4) or HNF-1alpha and express the progenitor marker OV-6. Interestingly, the EMT process confers them resistance to the apoptotic effect of TGF-beta, with cells showing higher levels of active AKT and Bcl-x(L) than fetal hepatocytes. In summary, these cells are refractory to the apoptotic effects of TGF-beta, showing characteristics of liver progenitors and of some hepatocellular carcinoma cells.
Assessment of intervertebral disc degeneration with magnetic resonance single‐voxel spectroscopy (2009)

This study examined the feasibility of using short-echo water-suppressed point-resolved spectroscopy (PRESS) on a clinical 3T magnetic resonance (MR) scanner for evaluating biochemical changes in degenerated bovine and cadaveric human intervertebral discs. In bovine discs (N = 17), degeneration was induced with papain injections. Degeneration of human cadaveric discs (N = 27) was assessed using the Pfirrmann grading on T(2)-weighted images. Chemicals in the carbohydrate region (Carb), the choline head group (Cho), the N-acetyl region (N-acetyl), and the lipid and lactate region (Lac+Lip) were quantified using (1)H PRESS, and were compared between specimens with different degrees of degeneration. The correlation between the spectroscopic findings and glycosaminoglycan (GAG) quantification using biochemical assays was determined. Significant differences were found between the ratios (N-acetyl/Cho, N-acetyl/Lac+Lip) acquired before and after papain injection in bovine discs. For human cadaveric discs, significant differences in the ratios (N-acetyl/Carb, N-acetyl/Lac+Lip) were found between discs having high and low Pfirrmann scores. Significant correlations were found between N-acetyl/Lac+Lip and GAG content in bovine discs (R = 0.77, P = 0.0007) and cadaveric discs (R = 0.83, P < 0.0001). Significant correlation between N-acetyl/Cho and GAG content was also found in cadaver discs (R = 0.64, P = 0.0039). This study demonstrates for the first time that short-echo PRESS on a clinical 3T MR scanner can be used to noninvasively and can reproducibly quantify metabolic changes associated with degeneration of intervertebral discs.