gebhart/patrepeval huggingface dataset:
Integration of Spectral Feature Extraction and Modeling for HMM-Based Speech Synthesis (2014)

This paper proposes a novel approach for integrating spectral feature extraction and acoustic modeling in hidden Markov model (HMM) based speech synthesis. The statistical modeling process of speech waveforms is typically divided into two component modules: the frame-by-frame feature extraction module and the acoustic modeling module. In the feature extraction module, the statistical mel-cepstral analysis technique has been used and the objective function is the likelihood of mel-cepstral coefficients for given speech waveforms. In the acoustic modeling module, the objective function is the likelihood of model parameters for given mel-cepstral coefficients. It is important to improve the performance of each component module for achieving higher quality synthesized speech. However, the final objective of speech synthesis systems is to generate natural speech waveforms from given texts, and the improvement of each component module does not always lead to the improvement of the quality of synthesized speech. Therefore, ideally all objective functions should be optimized based on an integrated criterion which well represents subjective speech quality of human perception. In this paper, we propose an approach to model speech waveforms directly and optimize the final objective function. Experimental results show that the proposed method outperformed the conventional methods in objective and subjective measures.
High throughput low latency LDPC decoding on GPU for SDR systems (2013)

In this paper, we present a high throughput and low latency LDPC (low-density parity-check) decoder implementation on GPUs (graphics processing units). The existing GPU-based LDPC decoder implementations suffer from low throughput and long latency, which prevent them from being used in practical SDR (software-defined radio) systems. To overcome this problem, we present optimization techniques for a parallel LDPC decoder including algorithm optimization, fully coalesced memory access, asynchronous data transfer and multi-stream concurrent kernel execution for modern GPU architectures. Experimental results demonstrate that the proposed LDPC decoder achieves 316 Mbps (at 10 iterations) peak throughput on a single GPU. The decoding latency, which is much lower than that of the state of the art, varies from 0.207 ms to 1.266 ms for different throughput requirements from 62.5 Mbps to 304.16 Mbps. When using four GPUs concurrently, we achieve an aggregate peak throughput of 1.25 Gbps (at 10 iterations).
Nuclear Factor 1 Synergizes with Progesterone Receptor on the Mouse Mammary Tumor Virus Promoter Wrapped around a Histone H3/H4 Tetramer by Facilitating Access to the Central Hormone-responsive Elements (2009)

Steroid hormones induce transcription of their responsive genes by complex mechanisms including synergism between the hormone receptors and other transcription factors. On the mouse mammary tumor virus (MMTV) promoter progesterone induction is mediated by the reciprocal synergism between progesterone receptor (PR) and the ubiquitous transcription factor nuclear factor 1 (NF1). PR binding mediates ATP-dependent displacement of histone H2A and H2B, enabling NF1 access to its target site. In minichromosomes assembled in vitro NF1 binding facilitates access of PR to the hormone-responsive elements (HREs) by precluding reforming of the histone octamer, but the function of NF1 in living cells remains unclear. Here we show that depleting NF1 by small interfering RNAs or mutating the NF1-binding site significantly compromises transcription of the MMTV promoter. The central HREs 2 and 3 are not needed for ATP-dependent H2A/H2B displacement or NF1 binding but are critical for full PR binding and MMTV transactivation. We found that NF1 binding to the MMTV promoter on a H3/H4 histone tetramer particle exposes the central HREs and facilitates their binding by PR, suggesting a possible mechanism for the reciprocal synergism between PR and NF1.
Interleukin-1 (IL-1) Pathway (2010)

The interleukin-1 (IL-1) family of cytokines comprises 11 proteins (IL-1F1 to IL-1F11) encoded by 11 distinct genes in humans and mice. IL-1-type cytokines are major mediators of innate immune reactions, and blockade of the founding members IL-1alpha or IL-1beta by the interleukin-1 receptor antagonist (IL-1RA) has demonstrated a central role of IL-1 in a number of human autoinflammatory diseases. IL-1alpha or IL-1beta rapidly increase messenger RNA expression of hundreds of genes in multiple different cell types. The potent proinflammatory activities of IL-1alpha and IL-1beta are restricted at three major levels: (i) synthesis and release, (ii) membrane receptors, and (iii) intracellular signal transduction. This pathway summarizes extracellular and intracellular signaling of IL-1alpha or IL-1beta, including positive- and negative-feedback mechanisms that amplify or terminate the IL-1 response. In response to ligand binding of the receptor, a complex sequence of combinatorial phosphorylation and ubiquitination events results in activation of nuclear factor kappaB signaling and the JNK and p38 mitogen-activated protein kinase pathways, which, cooperatively, induce the expression of canonical IL-1 target genes (such as IL-6, IL-8, MCP-1, COX-2, IkappaBalpha, IL-1alpha, IL-1beta, MKP-1) by transcriptional and posttranscriptional mechanisms. Of note, most intracellular components that participate in the cellular response to IL-1 also mediate responses to other cytokines (IL-18 and IL-33), Toll-like-receptors (TLRs), and many forms of cytotoxic stresses.
Germ Line Transmission of a Yeast Artificial Chromosome Spanning the Murine α 1 (I) Collagen Locus (1993)

Molecular complementation of mutant phenotypes by transgenic technology is a potentially important tool for gene identification. A technology was developed that allows the transfer of a physically intact yeast artificial chromosome (YAC) into the germ line of the mouse. A purified 150-kilobase YAC encompassing the murine gene Col1a1 was efficiently introduced into embryonic stem (ES) cells via lipofection. Chimeric founder mice were derived from two transfected ES cell clones. These chimeras transmitted the full length transgene through the germ line, generating two transgenic mouse strains. Transgene expression was visualized as nascent transcripts in interphase nuclei and quantitated by ribonuclease protection analysis. Both assays indicated that the transgene was expressed at levels comparable to the endogenous collagen gene.
Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber-associated immune deviation (2001)

Injection of antigen into the anterior chamber (AC) of the eye, an immunologically privileged site, is associated with the induction of immune deviation, as evidenced by T helper cell (Th) 1 to Th2 cell polarization. We recently demonstrated that AC-associated immune deviation (ACAID) is a thymus-dependent phenomenon initiated by the formation of regulatory alpha,beta T-cell receptor-positive CD4(-) CD8(-) thymocytes (THYregs). In this study, the afferent and efferent limbs of this immunoregulatory loop were traced from peripheral blood to the thymus and then to the spleen by adoptive-transfer assays. The results demonstrate that (1) F4/80(+) CD1(+) peripheral blood mononuclear cells from mice whose ACs were injected with trinitrophenol-bovine serum albumin induce the appearance of natural killer (NK) 1.1(+) THYreg in naïve recipients within 24 h of intravenous infusion; (2) these NK THYregs induce (or generate) suppressor-effector T cells in the spleens of adoptive recipients; (3) these suppressor-effector spleen cells, but not the NK THYregs themselves, directly inhibit the expression of delayed-type hypersensitivity in sensitized recipients; and (4) peripheral blood mononuclear cells from AC-injected mice do not induce ACAID in thymectomized recipients. These results confirm our hypothesis that ACAID is a model of centrally induced dominant tolerance mediated by CD-1-dependent NK T cells of recent thymic origin. The results also provide evidence of a novel tolerance induction pathway by which blood-borne antigen-presenting cells generated by antigen injection into an immunologically privileged site transport antigen to the thymus and induce the formation and export of THYreg.
A multilayered neural network controller (1988)

A multilayered neural network processor is used to control a given plant. Several learning architectures are proposed for training the neural controller to provide the appropriate inputs to the plant so that a desired response is obtained. A modified error-back propagation algorithm, based on propagation of the output error through the plant, is introduced. The properties of the proposed architectures are studied through a simulation example.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hindered Rotation in Diphenylmethane Derivatives. Electrostatic vs Charge-Transfer and Homoconjugative Aryl−Aryl Interactions (1998)

A series of p,p‘-disubstituted 7-phenyl-7-(2-fluorophenyl)norbornanes 5xy has been prepared, and the barrier (ΔG#) to 160° libration around the 2-fluoroaryl-norbornane bond has been measured by DNMR. There is spectroscopic evidence of strong homoconjugative and charge-transfer (CT) interactions between both aryl groups of 5xy. However, the relationship between ΔG# and the nature of the substituents X and Y is accounted for only by electrostatic interactions between both aryl groups in the ground state as well as in the transition state of the libration. Therefore, the notion of CT and aromatic homoconjugation as strong attractive forces between aryl groups should be definitively rejected.
Regulation of Bacterial Drug Export Systems (2002)

The active transport of toxic compounds by membrane-bound efflux proteins is becoming an increasingly frequent mechanism by which cells exhibit resistance to therapeutic drugs. This review examines the regulation of bacterial drug efflux systems, which occurs primarily at the level of transcription. Investigations into these regulatory networks have yielded a substantial volume of information that has either not been forthcoming from or complements that obtained by analysis of the transport proteins themselves. Several local regulatory proteins, including the activator BmrR from Bacillus subtilis and the repressors QacR from Staphylococcus aureus and TetR and EmrR from Escherichia coli, have been shown to mediate increases in the expression of drug efflux genes by directly sensing the presence of the toxic substrates exported by their cognate pump. This ability to bind transporter substrates has permitted detailed structural information to be gathered on protein-antimicrobial agent-ligand interactions. In addition, bacterial multidrug efflux determinants are frequently controlled at a global level and may belong to stress response regulons such as E. coli mar, expression of which is controlled by the MarA and MarR proteins. However, many regulatory systems are ill-adapted for detecting the presence of toxic pump substrates and instead are likely to respond to alternative signals related to unidentified physiological roles of the transporter. Hence, in a number of important pathogens, regulatory mutations that result in drug transporter overexpression and concomitant elevated antimicrobial resistance are often observed.
Inhibition of c-fms by Imatinib: Expanding the Spectrum of Treatment (2005)

Imatinib is a selective protein tyrosine kinase inhibitor currently used in the treatment of chronic myeloid leukaemia (CML). It specifically suppresses the growth of bcr-abl expressing CML progenitor cells by blocking the ATP-binding site of the kinase domain of bcr-abl. Imatinib also inhibits the c-abl, platelet derived growth factor receptor (PDGFR), abl-related gene and stem cell factor receptor, c-kit, protein tyrosine kinases. It is through inhibition of c-kit that imatinib is also used clinically in the treatment of gastrointestinal stromal tumours. We have recently demonstrated that imatinib also specifically targets the macrophage colony stimulating factor receptor, c-fms, at therapeutic concentrations. Although this finding has important implications with regard to potential side effects in patients currently receiving imatinib therapy, these results suggest that imatinib may also be useful in the treatment of diseases where c-fms is implicated. This includes breast and ovarian cancer and inflammatory conditions such as rheumatoid arthritis. We also speculate that imatinib may be used in diseases where bone destruction occurs due to excessive osteoclast activity, such as in the haematologic malignancy, multiple myeloma.
Accurate, efficient, and adaptive calling context profiling (2006)

Calling context profiles are used in many inter-procedural code optimizations and in overall program understanding. Unfortunately, the collection of profile information is highly intrusive due to the high frequency of method calls in most applications. Previously proposed calling-context profiling mechanisms consequently suffer from either low accuracy, high overhead, or both. We have developed a new approach for building the calling context tree at runtime, called adaptive bursting . By selectively inhibiting redundant profiling, this approach dramatically reduces overhead while preserving profile accuracy. We first demonstrate the drawbacks of previously proposed calling context profiling mechanisms. We show that a low-overhead solution using sampled stack-walking alone is less than 50% accurate, based on degree of overlap with a complete calling-context tree. We also show that a static bursting approach collects a highly accurate profile, but causes an unacceptable application slowdown. Our adaptive solution achieves 85% degree of overlap and provides an 88% hot-edge coverage when using a 0.1 hot-edge threshold, while dramatically reducing overhead compared to the static bursting approach.
Chemosensitivity of fine afferents from rat skin in vitro (1990)

1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)
Fecal Occult Blood Testing for Iron Deficiency: A Reappraisal (2000)

Fecal occult blood (FOB) tests have been evaluated primarily for the application of colorectal cancer screening. Less is known about the performance characteristics of FOB tests for the evaluation of iron deficiency, the most common other application. As most clinically important occult gastrointestinal bleeding arises from the proximal gut, it is critical that FOB tests target analytes that are stable during the enteric transit. Available data indicate that guaiac-type and immunochemical tests are insensitive for the detection of proximal gut bleeding, and their use may confound the evaluation of iron deficiency. In contrast, the heme porphyrin test is sensitive for both proximal and distal sources of occult gastrointestinal bleeding, and this FOB test would appear to be the most rational selection for use in patients with iron deficiency or anemia. Outcome data are needed to better assess the impact of FOB testing on algorithms for evaluation of iron deficiency.
Involvement of a Conserved Tryptophan Residue in the UDP-Glucose Binding of Large Clostridial Cytotoxin Glycosyltransferases (2000)

Large clostridial cytotoxins catalyze the glucosylation of Rho/Ras GTPases using UDP-glucose as a cosubstrate. By site-directed mutagenesis of Clostridium sordellii lethal toxin and Clostridium difficile toxin B fragments, we identified tryptophan 102, which is located in a conserved region within the catalytic domain of all clostridial cytotoxins, to be crucial for UDP-glucose binding. Exchange of Trp-102 with alanine decreased the glucosyltransferase activity by about 1,000-fold and blocked cytotoxic activity after microinjection. Replacement of Trp-102 by tyrosine caused a 100-fold reduction in enzyme activity, indicating a partial compensation of the tryptophan function by tyrosine. Decrease in glucosyltransferase and glycohydrolase activity was caused predominantly by an increase in the K(m) for UDP-glucose of these mutants. The data indicate that the conserved tryptophan residue is implicated in the binding of the cosubstrate UDP-glucose by large clostridial cytotoxins. Data bank searches revealed different groups of proteins sharing the recently identified DXD motif (Busch, C., Hofmann, F., Selzer, J., Munro, J., Jeckel, D., and Aktories, K. (1998) J. Biol. Chem. 273, 19566-19572) and a conserved region defined by a tryptophan residue equivalent to Trp-102 of C. sordellii lethal toxin. From our findings, we propose a novel family of glycosyltransferases which includes both prokaryotic and eukaryotic proteins.
Src Uses Cas to Suppress Fhl1 in Order to Promote Nonanchored Growth and Migration of Tumor Cells (2006)

Anchorage independence and motility are hallmarks of tumor cell growth. Tumor cell growth and morphology can be normalized by contact with nontransformed cells. The Src tyrosine kinase phosphorylates specific sites on the focal adhesion adaptor protein Crk-associated substrate (Cas) to promote nonanchored cell growth and migration. We studied the effects of Src and Cas on the expression of >14,000 genes to identify molecular events that underlie these activities. Gene expression in tumor cells that were normalized by neighboring nontransformed cells was used as an additional filter to identify genes that control metastatic cell growth. This process enabled the identification of genes that play roles in anchorage-independent cell growth and migration. One candidate, four and a half LIM domains 1 (Fhl1), acts as a transcriptional regulator that can associate with cell junctions as well as with the nucleus. We show here that Src phosphorylates Cas to block Fhl1 expression. In addition, suppression of Fhl1 is required for Src to promote tumor cell growth. These data show that Fhl1 is a tumor suppressor gene that acts downstream of Src and Cas to specifically block anchorage-independent cell growth and migration. Moreover, Fhl1 was suppressed in tumors from several human tissues. Thus, identification of how Fhl1 controls fundamental aspects of tumor cell growth and metastasis may lead to the development of novel markers that can be used to diagnose human clinical specimens as well as open innovative avenues of investigations aimed at developing reagents that target cancer cells while minimizing damage to normal cells.
Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican-3-derived peptide (2013)

Glypican-3 (GPC3), which is a carcinoembryonic antigen, is overexpressed in human hepatocellular carcinoma (HCC). Previously, we performed a phase I clinical trial of GPC3‑derived peptide vaccination in patients with advanced HCC, and reported that GPC3 peptide vaccination is safe and has clinical efficacy. Moreover, we proposed that a peptide‑specific CTL response is a predictive marker of overall survival in patients with HCC who receive peptide vaccination. In this study, we established GPC3‑derived peptide-specific CTL clones from the PBMCs of an HLA-A*02:07-positive patient with HCC who was vaccinated with an HLA-A2-restricted GPC3 peptide vaccine and showed a clinical response in the phase I clinical trial. Established CTL clones were analyzed using the IFN-γ ELISPOT assay and a cytotoxicity assay. GPC3 peptide-specific CTL clones were established successfully from the PBMCs of the patient. One CTL clone showed cytotoxicity against cancer cell lines that expressed endogenously the GPC3 peptide. The results suggest that CTLs have high avidity, and that natural antigen-specific killing activity against tumor cells can be induced in a patient with HCC who shows a clinical response to vaccination with the GPC3144-152 peptide.
The Rational Design of Vaccine Adjuvants for Mucosal and Neonatal Immunization (2001)

There is an urgent requirement for neonatal vaccines that induce effective and long-lasting immune responses at the mucosal surfaces of the gut and respiratory tract. The delay in their development has been due in part to a lack of understanding of the mucosal and neonatal immune systems. This work reviews recent advances in the understanding of the cells and molecules that mediate immunity, describing the importance of different T helper populations in determining the success of vaccination strategies. These advances have allowed the rational design of novel vaccine adjuvants and delivery systems that can selectively induce immunity at different anatomical sites mediated by distinct T cell populations. Five functional classes of adjuvant are described. These exploit mechanisms which a) create an antigen depot, b) preserve antigen conformation, c) direct antigen to specific immune cells, d) induce mucosal responses and e) induce cytotoxic T cell responses. Comparisons are made between the chemical structures of bacterial toxins and non-toxic derivatives that retain adjuvanticity. The concept of DNA immunization is introduced and the advantages and disadvantages of this novel approach are discussed. The specific problems relating to neonatal immunization are explored with particular reference to the functional immaturity of the neonatal immune system and interference by maternal antibody. Finally, recent work suggesting that there is no intrinsic barrier to designing effective neonatal vaccines deliverable by the mucosal route is discussed.