gebhart/patrepeval huggingface dataset:
Enabling alternating phase shifted mask designs for a full logic gate level (2002)

The International Technology Roadmap for Semiconductors lists F2 (157 nm exposure wavelength) optical lithography and extreme ultraviolet (EUV) next generation lithography as the two most feasible lithography solutions for the 70 nm technology node. It is very likely that both of these lithography solutions will be late, forcing ArF (193 nm exposure wavelength) lithography to operate at unprecedented resolution levels. Lithographically, alternating phase shifted masks (altPSM) can achieve the resolution required to manufacture 70 nm logic products with ArF lithography equipment [P. Schiavone, F. Lalanne, and A. Prola, "Clear field alternating PSM for 193 nm lithography," Proc. SPIE 3679, 582-589 (1999) and M. Fritz et al., "Application of chromeless phase-shift masks to sub-100 nm SOI CMOS transistor fabrication," Proc. SPIE 4000, 388-407 (2000)], but technical and logistical challenges associated with the broad implementation of altPSM require novel and invasive EDA solutions which have caused the industry to shy away from altPSM in the past. Since the resolution capabilities of altPSM are well understood in the lithography community, this paper will focus on the challenges facing altPSM implementation for the polysilicon gate level and will present the results of a detailed altPSM design feasibility study done at IBM for the 180 nm technology node. While the 70 nm technology node will push resolution harder then ever before, the design rules, EDA tools, and layout methodologies developed in the past lay the foundation for our attack on this challenging technology node.
Design of teleoperated surgical instruments for minimally invasive surgery (1998)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1998.
Endocrine tumors of the pancreas (2005)

Understanding the molecular events underlying the biology of pancreatic islet cell tumors will aid the development of accurate prognostic markers and will guide improved therapeutic modalities in the future.
Improved recombinant protein yield using a codon deoptimized DHFR selectable marker in a CHEF1 expression plasmid (2010)

The CHEF1 expression plasmid utilizes regulatory domains of the Chinese Hamster Elongation Factor 1 (CHEF1) housekeeping gene to drive stable recombinant protein expression in Chinese Hamster Ovary (CHO) cells. Rapid development of stable CHEF1 cell lines is possible, in part, because high titer pools are produced in the absence of methotrexate-induced DHFR amplification. Inhibiting DHFR activity with methotrexate increases the selection pressure on transfected cells and can result in a compensatory event to ensure cell survival, such as dhfr gene amplification or integration into a transcriptionally active genomic site. Methotrexate amplification often results in improved cell line productivity but it is a time-consuming process. Herein, we describe a novel mechanism to increase selection stringency via codon deoptimization of the mouse dhfr selectable marker utilizing hamster codon preference that results in improved expression of a linked recombinant protein compared to wild-type DHFR selection. We show that deoptimizing the translatability of the dhfr gene reduces the expression level of the DHFR protein in CHO transfection pools and derived clones. Lower DHFR expression increases the transfection selection stringency, shown as lower transfection efficiency in pools, and correlates with increased recombinant protein expression in both pools and clones. These results demonstrate a new mechanism for increasing selection stringency and improving recombinant protein production during cell line development without time-consuming gene amplification steps.
Biodegradable polymers and environmental interaction (1998)

Abstract Biodegradable polymers are by definition those that degrade as a result of the action of microorganisms and/or enzymes. The rate of this biodegradation may vary from hours to years depending on the molecular architecture of the polymer in question. Biopolymers like lignin take years to degrade while many proteins and polysaccharides degrade within hours to days. The same is true for the synthetic biodegradable polymers where polyethylene is sometimes regarded as inert to biodegradation while polyanhydrides are rapidly biodegradable. The influence of structure, morphology, and surface area on the biodegradability are discussed, with polyesters and degradable polyethylene (with pro‐oxidant and/or biodegradable additives) as examples. The rate of biodegradation is controllable by choosing the appropriate molecular architecture. In addition to this the environmental interaction of these polymers should be determined. The degradation product pattern of biodegradable polymers should be compatible with the natural degradation mechanisms (i.e., catabolisms).
The design and implementation of a high-bandwidth file service for continuous media (1991)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1991.
Evaluation of the Antitumor Efficacy of RNAi-Mediated Inhibition of CDC20 and Heparanase in an Orthotopic Liver Tumor Model (2015)

Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy.
Robust matrix rank reduction methods for seismic data processing (2013)

An important step of seismic data processing entails signal de-noising. Traditional de-noising methods assume Gaussian noise model and their performance degrades in the presence of erratic (non-Gaussian) noise. This thesis examines the problem of designing reduced-rank noise attenuation algorithms that are resistant to erratic noise. I first introduce a robust matrix factorization based on M-estimate and incorporate it into the formulation of the classical Singular Spectrum Analysis (SSA) algorithm. This new algorithm (Robust SSA) permits to de-noise seismic data that have been contaminated by non-Gaussian noise. I also propose a second Robust SSA algorithm that attacks the data de-noising and reconstruct problems as low-rank matrix recovery problem that is solved by a convex optimization algorithm. The NP-hard rank minimization problem is replaced by its tightest convex relaxation, the nuclear-norm minimization. An augmented Lagrangian method is used to numerically look for the solution that minimizes the cost function.
Immunolocalization of fibroblast growth factor receptor 1 and its ligands in human tissues. (1993)

We have been able to define the distribution of FGFR-1 and its ligands in normal human tissues. The results will be useful for determining the function of these growth factors and their receptors under both normal physiologic and pathologic conditions.
Cloning, Localization, and Functional Expression of Sodium Channel β1A Subunits (2000)

Auxiliary beta1 subunits of voltage-gated sodium channels have been shown to be cell adhesion molecules of the Ig superfamily. Co-expression of alpha and beta1 subunits modulates channel gating as well as plasma membrane expression levels. We have cloned, sequenced, and expressed a splice variant of beta1, termed beta1A, that results from an apparent intron retention event. beta1 and beta1A are structurally homologous proteins with type I membrane topology; however, they contain little to no amino acid homology beyond the shared Ig loop region. beta1A mRNA expression is developmentally regulated in rat brain such that it is complementary to beta1. beta1A mRNA is expressed during embryonic development, and then its expression becomes undetectable after birth, concomitant with the onset of beta1 expression. In contrast, beta1A mRNA is expressed in adult adrenal gland and heart. Western blot analysis revealed beta1A protein expression in heart, skeletal muscle, and adrenal gland but not in adult brain or spinal cord. Immunocytochemical analysis of beta1A expression revealed selective expression in brain and spinal cord neurons, with high expression in heart and all dorsal root ganglia neurons. Co-expression of alphaIIA and beta1A subunits in Chinese hamster lung 1610 cells results in a 2.5-fold increase in sodium current density compared with cells expressing alphaIIA alone. This increase in current density reflected two effects of beta1A: 1) an increase in the proportion of cells expressing detectable sodium currents and 2) an increase in the level of functional sodium channels in expressing cells. [(3)H]Saxitoxin binding analysis revealed a 4-fold increase in B(max) with no change in K(D) in cells coexpressing alphaIIA and beta1A compared with cells expressing alphaIIA alone. beta1A-expressing cell lines also revealed subtle differences in sodium channel activation and inactivation. These effects of beta1A subunits on sodium channel function may be physiologically important events in the development of excitable cells.
Target-based therapies in breast cancer: current status and future perspectives (2009)

Identification of molecular alterations in key proteins involved in breast cancer cell proliferation and survival resulted in the development of a new treatment strategy with target-based agents. The anti-ErbB-2 monoclonal antibody (mAb) trastuzumab and the dual epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor lapatinib are effective in patients with breast cancer that overexpresses ErbB-2. The anti-vascular endothelial growth factor-A mAb bevacizumab is approved in combination with taxanes for treatment of unselected patients with metastatic breast cancer. In addition, preclinical data suggest that signaling inhibitors can prevent or overcome resistance to endocrine therapy in estrogen receptor positive (ER+) breast cancer. However, the majority of signaling inhibitors explored in breast cancer patients has shown little activity, at least when used as monotherapy; and the results of clinical trials in ER+ breast cancer of combinations of signaling inhibitors and endocrine therapies are rather disappointing. Negative findings are likely due to mechanisms of intrinsic or acquired resistance to target-based agents. Breast carcinoma is a complex and heterogeneous disease and several different molecular alterations are involved in its pathogenesis and progression. The redundancy of oncogenic pathways activated in cancer cells, the heterogeneity of the mechanisms of resistance, and the plasticity of tumor cells that are capable to adapt to different growth conditions, significantly hamper the efficacy of each signaling inhibitor in breast cancer. Therefore, a comprehensive approach that takes into account the complexity of the disease is definitely required to improve the efficacy of target-based therapy in breast cancer.
Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy–Mediated Metastatic Melanoma Phenotype (2014)

This study provides evidence that BRAF inhibition promotes the adoption of a reversible, therapy-driven metastatic phenotype in melanoma. The cotargeting of ligand-independent EPHA2 signaling and BRAF may be one strategy to prevent the development of therapy-mediated disease at new sites.
Renal Expression of FGF23 in Progressive Renal Disease of Diabetes and the Effect of Ace Inhibitor (2013)

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF) and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE) inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.
Is ASR ready for wireless primetime: measuring the core technology for selected applications (2002)

It is estimated that by the end of 2001 as many as 500 million people worldwide will use cellular services. The nature of hands-busy and eyes-busy situations inherent in the anywhere and anytime wireless communication paradigm presents exciting marketing opportunities and, at the same time, unique technical challenges to the current-generation automatic speech recognition (ASR) technology and its new applications. Current industry trends clearly show that incorporating ASR technology into existing or new wireless services as a replacement for touch-tone input is a natural progression in the user interface. But is the current-generation ASR technology ready for primetime over wireless channels? Both qualitative and quantitative assessments for the core technology must be adopted by the industry before answering this question. In this paper, we describe a set of benchmark tasks designed to evaluate the state-of-the-art ASR technologies and present the results of these benchmark tests on two commercially available software-based ASR systems that represent the best core ASR technology on the market.
Deciphering antibody properties that lead to potent botulinum neurotoxin neutralization (2004)

Monoclonal antibodies (mAbs) have been developed that bind to the toxin binding domain (H(C)) of botulinum toxin type A. These mAbs recognize with high affinity nonoverlapping epitopes on native toxin. The potency of a combination of three of the mAbs is almost 100 times greater than that reported for human polyclonal botulinum immune globulin. Potency appears to result largely from a marked increase in binding affinity for toxin that results when antibodies are combined. Precise epitope, or even domain recognized, seems to be of much less importance. The very high affinity required for toxin neutralization suggests why single mAbs that potently neutralize toxin have not been reported. Such affinities are not typically generated by the immune response.
Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma (2001)

Various studies have demonstrated the aberrant expression of normal testicular proteins in neoplastic cells. These proteins collectively form the new class of tumor antigens called cancer-testis (CT) antigens. Their selective normal tissue expression makes them ideal antigens for immune targeting of the malignant disease. In this study, the expression of a spermatozoa protein, Sp17, in multiple myeloma was investigated. It was found that Sp17 is detectable in tumor cells from 12 of 47 (26%) myeloma patients. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis detected Sp17 transcripts and proteins, respectively. Northern blot analysis and RT-PCR demonstrated that Sp17 transcripts were detected only in normal testis, supporting its tissue specificity. Since a high proportion of normal individuals develop antibodies against Sp17 following vasectomy, Sp17 is likely to be a highly immunogenic protein in vivo. Sp17 is therefore a novel member of the CT antigen family and should be an ideal target for immunotherapy of multiple myeloma.
The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages (2002)

Abstract Monocytes, macrophages and dendritic cells play an important role in the initial infection and contribute to its pathogenesis throughout the course of infection. Myeloid cells express CD4 and chemokine receptors known for HIV‐1 fusion and entry. The β‐chemokine receptor, CCR5, is the major co‐receptor in conjunction with CD4 for macrophage (M)‐tropic or (R5) isolates of HIV‐1, whereas the α‐chemokine receptor, CXCR4, facilitates entry of T‐tropic or (X4) HIV‐1 strains. Cells of myeloid lineage may be infected predominantly with R5‐ strains, although infection with dual‐tropic isolates of HIV‐1 (exhibiting the capacity to use CCR‐5 and/or CXCR‐4 for entry) or some strains of X4‐ isolates has also been reported. The expression of chemokine receptors, HIV‐1 infectio n and replication is under continuous regulation by a complex cytokine network produced by a variety of cells. The effects of cytokines/chemokines on HIV‐1 replication in cells of myeloid lineage can be inhibitory (IFN‐α, IFN‐β, IFN‐γ, GM‐CSF, IL‐10, IL‐13 and IL‐16 and β‐chemok ines), stimulatory (M‐CSF, TNF‐α, TNF‐β, IL‐1, IL‐6) or bifunction al, that is both inhibitory and stimulatory (IL‐4). This review focuses on the overall expression of chemokine receptors on cells of myeloid lineage and considers the mechanisms of entry of R5‐, X4‐ and dual‐tropic strains of HIV‐1 into these cells. The effects of cytokines/chemokines on viral entry and productive HIV‐1 infection are also reviewed. Copyright © 2003 John Wiley &amp; Sons, Ltd.
Delayed protection by ESAT-6–specific effector CD4+ T cells after airborne M. tuberculosis infection (2008)

Mycobacterium tuberculosis infection induces complex CD4 T cell responses that include T helper type 1 (Th1) cells and regulatory T cells. Although Th1 cells control infection, they are unable to fully eliminate M. tuberculosis, suggesting that Th1-mediated immunity is restrained from its full sterilizing potential. Investigation into T cell-mediated defense is hindered by difficulties in expanding M. tuberculosis-specific T cells. To circumvent this problem, we cloned CD4(+) T cells from M. tuberculosis-infected B6 mice and generated transgenic mice expressing a T cell receptor specific for the immunodominant antigen early secreted antigenic target 6 (ESAT-6). Adoptively transferred naive ESAT-6-specific CD4(+) T cells are activated in pulmonary lymph nodes between 7 and 10 d after aerosol infection and undergo robust expansion before trafficking to the lung. Adoptive transfer of activated ESAT-6-specific Th1 cells into naive recipients before aerosol M. tuberculosis infection dramatically enhances resistance, resulting in 100-fold fewer bacteria in infected lungs. However, despite large numbers of Th1 cells in the lungs of mice at the time of M. tuberculosis challenge, protection was not manifested until after 7 d following infection. Our results demonstrate that pathogen-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection.
Herpes Simplex Virus Glycoprotein D Can Bind to Poliovirus Receptor-Related Protein 1 or Herpesvirus Entry Mediator, Two Structurally Unrelated Mediators of Virus Entry (1998)

Several cell membrane proteins have been identified as herpes simplex virus (HSV) entry mediators (Hve). HveA (formerly HVEM) is a member of the tumor necrosis factor receptor family, whereas the poliovirus receptor-related proteins 1 and 2 (PRR1 and PRR2, renamed HveC and HveB) belong to the immunoglobulin superfamily. Here we show that a truncated form of HveC directly binds to HSV glycoprotein D (gD) in solution and at the surface of virions. This interaction is dependent on the native conformation of gD but independent of its N-linked glycosylation. Complex formation between soluble gD and HveC appears to involve one or two gD molecules for one HveC protein. Since HveA also mediates HSV entry by interacting with gD, we compared both structurally unrelated receptors for their binding to gD. Analyses of several gD variants indicated that structure and accessibility of the N-terminal domain of gD, essential for HveA binding, was not necessary for HveC interaction. Mutations in functional regions II, III, and IV of gD had similar effects on binding to either HveC or HveA. Competition assays with neutralizing anti-gD monoclonal antibodies (MAbs) showed that MAbs from group Ib prevented HveC and HveA binding to virions. However, group Ia MAbs blocked HveC but not HveA binding, and conversely, group VII MAbs blocked HveA but not HveC binding. Thus, we propose that HSV entry can be mediated by two structurally unrelated gD receptors through related but not identical binding with gD.
Composition Changes of Peanut Fruit Parts During Maturation1 (1974)

Abstract Studies are reported which follow the changes in starch, sugar, fresh and extraction residue weights of peanut fruit parts during maturation. Observations are also reported on the lipid content of the seed. Starch and sugar contents reached maximum levels first in the pericarp (hull) and then the seed coat (testa). Starch maxima occurred at early and middle maturity (stages 3 [10 mg] and 7 [10 mg]) and sugar maxima at a stage approaching middle maturity and at middle maturity (stage 6 [47 mg] and 8[9 mg]), respectively. In the seed, starch reached a maximum just beyond middle maturity (stage 9 [55 mg]) and then remained constant. Sugar content increased throughout maturation and lipid content became maximum at full maturity (stage 13 [415 mg]) then declined to 385 mg at over-maturity (stage 15). The role of regulating substrate supply to the developing seed seemed to shift from the pericarp to the seed coat with increasing maturity. Observed increases in fruit residue weight suggest that the pericarp is competing with the seed for metabolic resources during the late maturity stages.