gebhart/patrepeval huggingface dataset:
Sharp profiles with high and low doping levels in silicon grown by molecular beam epitaxy (1981)

We find that heavy adsorbed dopant layers, up to several tens of equivalent monolayers, can be made to produce heavily doped n (Sb) and p (Ga) layers in molecular beam epitaxy grown silicon. By preadjusting the adlayer concentration to the required value while temporarily arresting silicon growth, arbitrarily sharp profiles of any sequence of dopant type with very high or low levels can be grown. Examples are given of p+ i p+ and n++p+ pp+ structures grown with transition thickness L?300 Å, and with controlled layer thicknesses of ∼1000 Å. Such structures, difficult to achieve otherwise, should be ideal for fabrication of high-frequency millimeter wave devices.
Who Is At the Door (1997)

The SYN Denial of Service: What SYN really is, why it's needed in TCP/IP, why the denial of service attack works and how to prevent it
Ecology and Behavior (1993)

PRINCIPLES OF ECOLOGY. 1. Animal Behavior. 2. Population Ecology. 3. Community Structure and Biodiversity. 4. Ecosystems. 5. The Biosphere
Suppression of tumor cell growth by syndecan-1 ectodomain. (1994)

Syndecans are integral membrane proteoglycans characterized by the similarity of cytoplasmic and transmembrane domains of the core proteins.Syndecans may regulate cell behavior by participating in matrix recognition and growth factor binding.Using syndecan-1 deletion mutants, we show that the extracellular part of the molecule (ectodomain) can suppress malignant growth, stimulate actin polymerization, and induce epithelioid morphology in mouse mammary tumor Shionogi 115 (5115) cells.Free ectodomain isolated from the culture medium of either syndecan-l-transfected 5115 cells or normal murine mammary gland (NMuMG) cells can suppress the growth of 5115 tumor cells at nanomolar concentrations.The ectodomain of syndecan-1 inhibited also the growth of other carcinoma cell lines, such as CarB and MCF-7, but no such inhibition was observed for contact-inhibited cell lines, including NIH 3T3 cells, NMuMG cells, and human HaCaT keratinocytes.Intact heparan sulfate structure of the ectodomain was required for the suppression because degradation of heparan sulfate chains completely abolished growth inhibition.These results suggest a tumor suppressor activity for the syndecan-1 ectodomain.Cell differentiation is based on the selective use of genetic information in response of extracellular stimuli; examples include cellular interactions and binding of extracellular effector molecules by cell surface receptors.Syndecans are cell surface proteoglycans (PGs),' which have been shown to participate in both matrix recognition and growth factor binding (1, 2) and thus may participate in cell regulation.The first member of this family to be described, syndecan-1, is found mainly on the
Heat Shock Proteins and Autoimmunity in Patients with Carotid Atherosclerosis (2007)

Studies aimed at elucidating the pathogenetic mechanisms underlying the initiation and progression of human atherosclerosis have emphasized the central role of inflammatory and immune cells. Atherosclerotic plaques are infiltrated by activated macrophages, T and B lymphocytes, plasma cells, and mast cells, releasing inflammatory molecules, which amplify the severity of the disease. Endothelial cells subjected to various stress conditions express increased amounts of heat shock proteins (HSPs), some of the most successfully conserved proteins throughout evolution. Many experimental observations reviewed in this article draw attention to several HSPs targeted by a specific cellular and humoral immune response in patients with atherosclerotic disease. The review also reports preliminary data obtained by our group on the possible role of HSP90 as a candidate autoantigen in carotid atherosclerosis. Our study deals with the presence of specific antibodies and T cells directed against HSP90 in patients with carotid atherosclerotic plaques. In 60% of these subjects' sera but in none of the sera from healthy controls immunoblotting (IB) detected the presence of specific antibodies. Moreover, 20% of peripheral blood mononuclear cells (PBMC) samples from patients but none from healthy subjects proliferated in response to human purified HSP90. In vitro experiments showed an upregulation of HSP90 expression in endothelial cells exposed to oxidative stress by treatment with H(2)O(2) and greater release of soluble HSP90 in culture supernatants from H(2)O(2)-treated cells than from untreated cells.
Synthetic circular RNA for protein expression (2019)

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Modeling and transient simulation of planes in electronic packages (2000)

This paper presents a modeling and simulation approach for ground/power planes in high speed packages. A plane pair structure is first characterized in terms of its impedance (Z) matrix at arbitrary port locations in the frequency domain. This solution is then extended for multiple plane pairs under the assumption that skin effect is prominent at higher frequencies causing isolation between the layers. Since the solutions are in analytical form, the frequency and transient response can be computed efficiently requiring small computational time. To develop spice models, equivalent circuits are constructed using resonator models with passive elements using model order reduction methods. This paper also discusses a method for incorporating decoupling capacitors into the plane models. The simulation results show good correlation with measured data.
Platelet Hyperreactivity and Prognosis in Survivors of Myocardial Infarction (1990)

We tested the hypothesis that an increase in spontaneous aggregability of platelets in vitro predicts mortality and coronary events in patients who have survived a recent myocardial infarction. A cohort of 149 survivors of infarction entered our study three months after the index infarction and was followed for five years. At entry and at intervals of six months, spontaneous platelet aggregation (SPA) was tested and graded as positive (aggregation within 10 minutes), intermediate (aggregation after 10 to 20 minutes), or negative (no aggregation within 20 minutes). During follow-up, 6.4 percent (6 of 94) of the patients in the SPA-negative group died, as compared with 10.3 percent (3 of 29) in the SPA-intermediate group and 34.6 percent (9 of 26) in the SPA-positive group. As compared with the SPA-negative group, the SPA-intermediate group had a relative risk of death of 1.6 (95 percent confidence interval, 0.5 to 5.5) and the SPA-positive group had a risk of 5.4 (95 percent confidence interval, 2.2 to 13.4). At least one cardiac event (cardiac death or recurrent nonfatal myocardial infarction) occurred in 14.9 percent (14 of 94 patients) of the SPA-negative group, 24.1 percent (7 of 29) of the SPA-intermediate group, and 46.2 percent (12 of 26) of the SPA-positive group. A positive test result continued to have prognostic value throughout the five-year study. We conclude that spontaneous platelet aggregation in vitro is a useful biologic marker for the prediction of coronary events and mortality in this low-risk group of survivors of a myocardial infarction. A causal relation is suggested but not proved by our study.
Expression of human interferon alpha H, an interferon with two potential asparagine-linked glycosylation sites. (1988)

Of the large number of human alpha interferon genes identified, only one, Hu-IFN-alpha H, contains potential asparagine-linked glycosylation sites. With the use of a new vector that permits convenient expression, site-specific mutation, and DNA sequencing, Hu-IFN-alpha H was expressed in Escherichia coli. The bacterial product which is not glycosylated is fully active demonstrating that the carbohydrate on this species is not required for antiviral activity.
The T-box gene family (1998)

A novel family of transcription factors that appears to play a critical role in the development of all animal species was recently uncovered on the basis of homology of the DNA binding domain of the Brachyury, or T locus, gene product. Phylogenetic studies have shown the ancient origin of this gene family, which has been named the T-box family, prior to the divergence of metazoa from a common ancestral type. T-box genes have now been identified in the genomes of C. elegans, Drosophila, sea urchin, ascidian, amphioxus, Xenopus, chick, zebrafish, mouse, and human and will probably be found in the genomes of all animals. Although functional analyses of T-box family members have just begun, the results show a wide range of roles in developmental processes that extend over time from the unfertilized egg through organogenesis. Only a few mutations in T-box genes are known, but all have drastic effects on development, including a targeted mutation in mice causing an embryonic lethal phenotype, and two human T-box gene mutations that results in developmental syndromes. This review presents a current overview of progress made in the analysis of T-box genes and their products in a variety of model systems.
Identification of a cloned sequence activated during multi-stage carcinogenesis in mouse skin (1991)

Differential screening of cDNA libraries made from chemically induced malignant mouse skin squamous cell carcinomas (SCC) identified three sequences, including one called mal2, that were upregulated in their expression at both the benign papilloma and malignant SCC stages. The mal2 plasmid cDNA clone (containing a 350 bp insert) was used to screen lambda phage cDNA libraries made from chemically induced SCCs. Two of the largest mal2-related cDNA inserts obtained from the phage libraries were sequenced. In addition a mal2-related genomic clone was obtained by hybridization probing of a mouse spleen genomic DNA library. The sequence of the genomic clone overlapped and was identical with both the mal2 plasmid and lambda cDNA clones. Identity was found between the mal2 cDNAs, the mal2 genomic sequence and the cDNA sequence for a mouse hyperproliferative keratin called K6. A synthetic oligonucleotide specific for the 3' untranslated region of the mal2 or keratin K6 gene was used in Northern analyses to demonstrate elevated steady-state levels of K6 keratin transcripts in SCCs induced by various protocols involving both chemical and ionizing radiation initiation of tumors as well as complete chemical and radiation carcinogenesis protocols. Metastatic lung lesions derived from SCCs generated by repeated doses of benzo[a]pyrene showed moderate levels of K6 keratin transcripts, whereas normal lung showed very low levels of K6 transcripts. The overexpression of the mal2 or keratin K6 gene in malignant SCCs was independent of the protocol, either chemical or radiation, that was used to induce the tumors.
CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool (2015)

Engineering of the CRISPR/Cas9 system has opened a plethora of new opportunities for site-directed mutagenesis and targeted genome modification. Fundamental to this is a stretch of twenty nucleotides at the 5' end of a guide RNA that provides specificity to the bound Cas9 endonuclease. Since a sequence of twenty nucleotides can occur multiple times in a given genome and some mismatches seem to be accepted by the CRISPR/Cas9 complex, an efficient and reliable in silico selection and evaluation of the targeting site is key prerequisite for the experimental success. Here we present the CRISPR/Cas9 target online predictor (CCTop, http://crispr.cos.uni-heidelberg.de) to overcome limitations of already available tools. CCTop provides an intuitive user interface with reasonable default parameters that can easily be tuned by the user. From a given query sequence, CCTop identifies and ranks all candidate sgRNA target sites according to their off-target quality and displays full documentation. CCTop was experimentally validated for gene inactivation, non-homologous end-joining as well as homology directed repair. Thus, CCTop provides the bench biologist with a tool for the rapid and efficient identification of high quality target sites.
A Flexible, Event-Driven Digital Filter With Frequency Response Independent of Input Sample Rate (2014)

This paper presents a clockless digital filter able to process inputs of different rates and formats, synchronous or asynchronous, with no adjustment needed to handle each input type. The filter is designed using a mix of asynchronous and real-time digital hardware, and for this reason relies on neither a clock nor the input data rate for setting its frequency response. The modular architecture of the filter, including delay segments with separated data and timing paths and a pipelined multi-way adder, allows easy extensions for different data widths. The filter was used as part of an ADC/DSP/DAC system which maintains its frequency response intact for varying sample rates without requiring any internal change. This property is not possible for any synchronous DSP system. The 16-tap, 8-bit FIR filter, integrated in a 130 nm CMOS process, includes on-chip automatic delay tuning, and for certain inputs, has signal-to-error ratio which exceeds that of clocked systems.
Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells (2001)

To improve the accuracy of predicting membrane protein sorting signals, we developed a general methodology for defining trafficking signal consensus sequences in the environment of the living cell. Our approach uses retroviral gene transfer to create combinatorial expression libraries of trafficking signal variants in mammalian cells, flow cytometry to sort cells based on trafficking phenotype, and quantitative trafficking assays to measure the efficacy of individual signals. Using this strategy to analyze arginine- and lysine-based endoplasmic reticulum localization signals, we demonstrate that small changes in the local sequence context dramatically alter signal strength, generating a broad spectrum of trafficking phenotypes. Finally, using sequences from our screen, we found that the potency of di-lysine, but not di-arginine, mediated endoplasmic reticulum localization was correlated with the strength of interaction with alpha-COP.
Immune-Based Therapies Targeting Mage-A4 for Relapsed/Refractory Hodgkin's Lymphoma After Stem Cell Transplant. (2009)

Abstract Abstract 4089 Poster Board III-1024 Stem cell transplantation (SCT) from autologous and, recently, allogeneic (unrelated adult donor and umbilical cord blood) sources is the treatment of choice for patients with relapsed/refractory Hodgkin's Lymphoma (HL). However, HL patients who relapse after SCT have limited options for long-term cure – necessitating the development of novel therapies for the treatment of this disease. We have previously shown that infusion of cytotoxic T cells (CTLs) targeting Epstein Barr virus (EBV)-derived proteins induced complete remissions in EBV+ HL patients. Unfortunately, approximately 70% of relapsed HL tumors are EBV-negative. Therefore, we investigated another promising T cell target, the cancer/testis antigen (CTA) MAGE-A4 as a potential target for CTL therapy. We hypothesize that adoptive transfer of MAGE-A4-specific T cells may be a feasible therapeutic strategy for patients with relapsed HL after SCT. MAGE-A4 is expressed by &gt;30% of EBV antigen-negative HL tumors and expression can be enhanced in MAGE-A4-negative tumors by epigenetic modification using HDAC inhibitors/demethylating agents that are currently in clinical use. We therefore determined whether MAGE-A4-specific cytotoxic T lymphocytes (CTL) could be expanded from healthy adult donor peripheral blood (PB) (n=9), cord blood (CB) (n=2) and HL patient blood (n=3). Dendritic cells (DCs) pulsed with overlapping peptides spanning MAGE-A4 were used as antigen presenting cells to stimulate peripheral blood mononuclear cells in the presence of IL-7, IL-12, and IL-15. After 9-12 days in culture, cells were stimulated weekly (with at least one additional stimulation) with MAGE-A4 peptide-pulsed DCs in the presence of IL7 and IL2. Analysis of the stimulated T cells using interferon gamma (IFN-γ) ELISPOT assays showed high specificity against MAGE-A4 with mean 96.6 (range 11-716) IFNγ-secreting spot forming cells (SFC)/10e5 cells in response to MAGE-A4 peptides compared to a mean of 7.8 (range 0-46.5) SFC/10e5 cells in response to irrelevant peptides. In addition, specific killing was measured in chromium (Cr51) release assays following co-culture with MAGE-A4 positive targets, showing that we successfully generated cytotoxic T cells. All evaluable T cell lines generated from healthy adult donors were predominantly CD8+, and 4 of the 8 showed specificity for a single, previously uncharacterized MAGE A4 epitope (aa266-285, NPARYEFLWGPRALAETSYV). In contrast, 6/8 T-cell lines derived from HL patients and CB were predominantly CD4+, and showed a range of MAGE-A4 epitope specificities. Mechanisms for these differences are now being investigated. These early results suggest that strategies using healthy donor cord blood and patient T cells for adoptive immunotherapy may be a novel and feasible approach for the treatment of relapsed HL post SCT. Disclosures: No relevant conflicts of interest to declare.
Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation (2009)

Oxygen level in mammalian cell culture is often controlled by placing culture vessels in humidified incubators with a defined gas phase partial pressure of oxygen (pO(2gas)). Because the cells are consuming oxygen supplied by diffusion, a difference between pO(2gas) and that experienced by the cells (pO(2cell)) arises, which is maximal when cells are cultured in vessels with little or no oxygen permeability. Here, we demonstrate theoretically that highly oxygen-permeable silicone rubber membranes can be used to control pO(2cell) during culture of cells in monolayers and aggregates much more accurately and can achieve more rapid transient response following a disturbance than on polystyrene and fluorinated ethylene-propylene copolymer membranes. Cell attachment on silicone rubber was achieved by physical adsorption of fibronectin or Matrigel. We use these membranes for the differentiation of mouse embryonic stem cells to cardiomyocytes and compare the results with culture on polystyrene or on silicone rubber on top of polystyrene. The fraction of cells that are cardiomyocyte-like increases with decreasing pO(2) only when using oxygen-permeable silicone membrane-based dishs, which contract on silicone rubber but not polystyrene. The high permeability of silicone rubber results in pO(2cell) being equal to pO(2gas) at the tissue-membrane interface. This, together with geometric information from histological sections, facilitates development of a model from which the pO(2) distribution within the resulting aggregates is computed. Silicone rubber membranes have significant advantages over polystyrene in controlling pO(2cell), and these results suggest they are a valuable tool for investigating pO(2) effects in many applications, such as stem cell differentiation.
Antibody light chain variable domains and their biophysically improved versions for human immunotherapy (2013)

We set out to gain deeper insight into the potential of antibody light chain variable domains (VLs) as immunotherapeutics. To this end, we generated a naïve human VL phage display library and, by using a method previously shown to select for non-aggregating antibody heavy chain variable domains (VHs), we isolated a diversity of VL domains by panning the library against B cell super-antigen protein L. Eight domains representing different germline origins were shown to be non-aggregating at concentrations as high as 450 µM, indicating VL repertoires are a rich source of non-aggregating domains. In addition, the VLs demonstrated high expression yields in E. coli, protein L binding and high reversibility of thermal unfolding. A side-by-side comparison with a set of non-aggregating human VHs revealed that the VLs had similar overall profiles with respect to melting temperature (T(m)), reversibility of thermal unfolding and resistance to gastrointestinal proteases. Successful engineering of a non-canonical disulfide linkage in the core of VLs did not compromise the non-aggregation state or protein L binding properties. Furthermore, the introduced disulfide bond significantly increased their T(m)s, by 5.5-17.5 ° C, and pepsin resistance, although it somewhat reduced expression yields and subtly changed the structure of VLs. Human VLs and engineered versions may make suitable therapeutics due to their desirable biophysical features. The disulfide linkage-engineered VLs may be the preferred therapeutic format because of their higher stability, especially for oral therapy applications that necessitate high resistance to the stomach's acidic pH and pepsin.
Disk drive reliability case study: dependence upon head fly-height and quantity of heads (2003)

Disk drive failure data is analyzed to gain insight regarding two significant concerns. The first is whether drive reliability is highly dependent on the number of read/write heads in a disk drive. Analyses separate drives by family so that the number of heads in the drive is the single uncontrolled variable. Drives are found to have multiple failure mechanisms vying for dominance in the early life. These analyses indicate a clear dependence between reliability and the number of read/write heads. For one family there is a very strong dependence, but for the second family it is much weaker. The second concern is whether the advances in design technology and manufacturing processes are progressing fast enough to counteract the potential reliability problems associated with consistently lowered head fly-height. The analysis shows that the positive impact of technology on drive reliability is far greater than any negative effect of a lower fly-height. That is, even though the more recent drives, have lower fly-heights, they are more reliable.
Colocation of Genes Encoding a tRNA-mRNA Hybrid and a Putative Signaling Peptide on Complementary Strands in the Genome of the Hyperthermophilic BacteriumThermotoga maritima (2006)

In the genome of the hyperthermophilic bacterium Thermotoga maritima, TM0504 encodes a putative signaling peptide implicated in population density-dependent exopolysaccharide formation. Although not noted in the original genome annotation, TM0504 was found to colocate, on the opposite strand, with the gene encoding ssrA, a hybrid of tRNA and mRNA (tmRNA), which is involved in a trans-translation process related to ribosome rescue and is ubiquitous in bacteria. Specific DNA probes were designed and used in real-time PCR assays to follow the separate transcriptional responses of the colocated open reading frames (ORFs) during transition from exponential to stationary phase, chloramphenicol challenge, and syntrophic coculture with Methanococcus jannaschii. TM0504 transcription did not vary under normal growth conditions. Transcription of the tmRNA gene, however, was significantly up-regulated during chloramphenicol challenge and in T. maritima bound in exopolysaccharide aggregates during methanogenic coculture. The significance of the colocation of ORFs encoding a putative signaling peptide and tmRNA in T. maritima is intriguing, since this overlapping arrangement (tmRNA associated with putative small ORFs) was found to be conserved in at least 181 bacterial genomes sequenced to date. Whether peptides related to TM0504 in other bacteria play a role in quorum sensing is not yet known, but their ubiquitous colocalization with respect to tmRNA merits further examination.