gebhart/patrepeval huggingface dataset:
Electromigration study of 50 &#x00B5;m pitch micro solder bumps using four-point Kelvin structure (2009)

Electromigration (EM) of micro bumps of 50 mum pitch was studied using four-point Kelvin structure. Two kinds of bumps, i. e., SnAg solder bump and Cu post with SnAg solder were tested. These bumps with thick Cu under bump metallization (UBM) were bonded with electroless Ni/Au (ENIG) pads. The results showed different EM features comparing with larger flip chip joints. Under various test temperatures from 100 to 140degC, the increasing of electrical resistance under current stressing was mainly due to the formation of the high temperature intermetallic compounds (IMCs). The resistance increase-rate in solder bump interconnects was faster than that of Cu post with SnAg bump joints since there was more low temperature solder and under current stressing, more IMCs would be formed. When Cu post with SnAg bumps were tested at 140degC with the current density of 4.08times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , after certain stressing time the resistances would reach a plateau region, where the diffusion between different materials, i. e., Cu, Ni and Sn reached equilibrium, and IMCs became stable. Large number of Kirkendall voids and a number of cracks were found in the Cu post interconnects which was caused by the electron wind since less voids and cracks were found in the adjacent bump interconnects. When Cu post with SnAg bumps were tested at 140degC with the current density of 2.04times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> for 1000 h, the resistance did not reach steady state. The electron flow direction also has an effect on the diffusion of materials. The degradation of resistance increased faster when electrons flow from Cu UBM to ENIG.
LABAZ1: A metastatic tumor model for renal cell carcinoma expressing the carbonic anhydrase type 9 tumor antigen. (2003)

A metastatic renal cell carcinoma (RCC) tumor model xenograft that expresses the targetable, membrane-bound tumor-associated antigen carbonic anhydrase type 9 (CA IX) is described. The xenograft, established from a high-grade type-2 chromophil RCC (cRCC), has been serially transplanted in immune compromised mice, in which it grows orthotopically under the renal capsule, doubling its size every 9 weeks and sending metastases to the lung and liver at approximately 20 weeks. Tumors were capable of being imaged using a micro-PET (micro-positron emission tomograph) with an 18-fluorodeoxyglucose (18-FDG) tracer. Subsequent xenograft generations have conserved immunohistochemical and ultrastructural properties typical for malignant renal epithelium-derived neoplasia (vimentin+, CK-19+, CA IX+ with hypoxia-inducible factor (HIF)-1 alpha constitutive expression) and have demonstrated extensive proliferation, lack of apoptosis, severe genetic alterations, and molecular expression alterations; transforming growth factor beta 1 (TGF-beta 1), hepatocyte growth factor (HGF), proto-oncogene (c-met), matrix metalloproteinase (MMP)-1, and vascular endothelial growth factor (VEGF) C and D were overexpressed, whereas human epidermal growth factor receptor (HER)-2, MMP-2 and MMP-9, VEGF-R3, p53, and p27 were severely down-regulated, suggesting a proangiogenic environment, local invasiveness, and facilitated lymphatic metastasis. Altogether, LABAZ1 provides a relevant and flexible model to study the biology of cRCC, the role of CA IX in RCC tumorigenesis, progression, and metastasis, and a platform for testing new targeted therapeutic strategies.
Cloning and functional expression in Escherichia coli of a cyanobacterial gene for lycopene cyclase, the enzyme that catalyzes the biosynthesis of β‐carotene (1993)

Carotenoids with cyclic end groups are essential components of the photosynthetic membrane in all known oxygenic photosynthetic organisms. These yellow pigments serve the vital role of protecting against potentially lethal photo-oxidative damage. Many of the enzymes and genes of the carotenoid biosynthetic pathway in cyanobacteria, algae and plants remain to be isolated or identified. We have cloned a cyanobacterial gene encoding lycopene cyclase, an enzyme that converts the acyclic carotenoid lycopene to the bicyclic molecule beta-carotene. The gene was identified through the use of an experimental herbicide, 2-(4-methylphenoxy)triethylamine hydrochloride (MPTA), that prevents the cyclization of lycopene in plants and cyanobacteria. Chemically-induced mutants of the cyanobacterium Synechococcus sp. PCC7942 were selected for resistance to MPTA, and a mutation responsible for this resistance was mapped to a genomic DNA region of 200 bp by genetic complementation of the resistance in wild-type cells. A 1.5 kb genomic DNA fragment containing this MPTA-resistance mutation was expressed in a lycopene-accumulating strain of Escherichia coli. The conversion of lycopene to beta-carotene in these cells demonstrated that this fragment encodes the enzyme lycopene cyclase. The results indicate that a single gene product, designated lcy, catalyzes both of the cyclization reactions that are required to produce beta-carotene from lycopene, and prove that this enzyme is a target site of the herbicide MPTA. The cloned cyanobacterial lcy gene hybridized well with genomic DNA from eukaryotic algae, thus it will enable the identification and cloning of homologous genes for lycopene cyclase in algae and plants.
Enhanced resistance to soybean cyst nematode Heterodera glycines in transgenic soybean by silencing putative CLE receptors (2015)

CLE peptides are small extracellular proteins important in regulating plant meristematic activity through the CLE-receptor kinase-WOX signalling module. Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem) and vascular cambium are controlled by CLE signalling pathways. Interestingly, plant-parasitic cyst nematodes secrete CLE-like effector proteins, which act as ligand mimics of plant CLE peptides and are required for successful parasitism. Recently, we demonstrated that Arabidopsis CLE receptors CLAVATA1 (CLV1), the CLAVATA2 (CLV2)/CORYNE (CRN) heterodimer receptor complex and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), which transmit the CLV3 signal in the SAM, are required for perception of beet cyst nematode Heterodera schachtii CLEs. Reduction in nematode infection was observed in clv1, clv2, crn, rpk2 and combined double and triple mutants. In an effort to develop nematode resistance in an agriculturally important crop, orthologues of Arabidopsis receptors including CLV1, CLV2, CRN and RPK2 were identified from soybean, a host for the soybean cyst nematode Heterodera glycines. For each of the receptors, there are at least two paralogues in the soybean genome. Localization studies showed that most receptors are expressed in the root, but vary in their level of expression and spatial expression patterns. Expression in nematode-induced feeding cells was also confirmed. In vitro direct binding of the soybean receptors with the HgCLE peptide was analysed. Knock-down of the receptors in soybean hairy roots showed enhanced resistance to SCN. Our findings suggest that targeted disruption of nematode CLE signalling may be a potential means to engineer nematode resistance in crop plants.
Apo2L/TRAIL and Bcl-2–related proteins regulate type I interferon–induced apoptosis in multiple myeloma (2001)

It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.
Spectral Signatures of Hydrated Proton Vibrations in Water Clusters (2005)

The ease with which the pH of water is measured obscures the fact that there is presently no clear molecular description for the hydrated proton. The mid-infrared spectrum of bulk aqueous acid, for example, is too diffuse to establish the roles of the putative Eigen (H3O+) and Zundel (H5O2+) ion cores. To expose the local environment of the excess charge, we report how the vibrational spectrum of protonated water clusters evolves in the size range from 2 to 11 water molecules. Signature bands indicating embedded Eigen or Zundel limiting forms are observed in all of the spectra with the exception of the three- and five-membered clusters. These unique species display bands appearing at intermediate energies, reflecting asymmetric solvation of the core ion. Taken together, the data reveal the pronounced spectral impact of subtle changes in the hydration environment.
Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. (1988)

TNF is a protein toxin which is secreted by activated macrophages and monocytes. Although the cytotoxic activity of TNF has been well documented, the mechanism of TNF-induced lysis is not well understood. The goal of this investigation was to determine whether TNF caused one of the classic forms of cell death, i.e., apoptosis, which is characterized by nuclear disintegration and cytoplasmic "boiling," or necrosis, which is characterized by the formation of a "balloon-like" plasma membrane and a lack of nuclear disintegration. Therefore, to distinguish apoptosis from necrosis, we have used time-lapse video microscopy to observe the death of several TNF-sensitive target cell lines while measuring the release of Na2(51)CrO4 and [3H]TdR from cytoplasmic and nuclear compartments, respectively. As targets we selected two spontaneously sensitive cell lines, F17 and L-M, and one resistant cell line, C3HA, which was sensitized by treatment with cycloheximide or by infection with the adeno-SV40 hybrid virus Ad2+ND2. We find that the type of cell death observed depends on the cell being tested. For example, in F17 cells we found that TNF treatment induced a classical form of apoptosis. In contrast, TNF induced a necrotic form of cell death in L-M cells, similar to the lysis induced by antibody and C. Finally, we found that sensitized C3HA cells displayed a novel cytolytic phenotype which resembled apoptosis but did not include DNA fragmentation. These results emphasize the complex nature of the TNF-induced cytotoxic response.
[Two scientific controversies shaping the development of surgery in the 20th century]. (2000)

By way of example, two scientific controversies that played a decisive role in shaping and determining the development--in the areas of chest and trauma surgery--of 20th century surgery, were discussed. In the former area, the spectacular method involving the use of a negative-pressure chamber, developed by Sauerbruch in 1904 was described--an innovation representing an enormous step forward in the field of surgery on the chest. However, the method failed to find widespread favour, and the opposite concept involving the use of positive-pressure was developed, and intratracheal ventilation--already under discussion at the beginning of the 20th century--finally won the day, and still remains in use. Medullary nailing of bone fractures as introduced by Küntscher initially prompted controversial discussion and at first appeared to have been rejected--only to find widespread acceptance nevertheless. It continues to be a justified method of achieving a stable osteosynthesis which, thanks to methodological refinements and improvements over the years, is an important option in the list of indications for surgical treatment of bone fractures. All in all, the following remark would appear applicable: An achievement alone does not suffice--someone is needed to recognize and endorse it.
Endogenous anti-inflammatory substances, inter-α-inhibitor and bikunin (2006)

There have been new developments in the elucidation of the biological functions of the inter-alpha-inhibitor (IalphaI) family. The anti-proteolytic activity of the IalphaI family originates from bikunin (also known as urinary trypsin inhibitor). Growing evidence indicates that bikunin is not just an anti-proteolytic agent, but can also be considered an anti-inflammatory agent that suppresses lipopolysaccharide (LPS)-induced cytokine synthesis. Bikunin functions to inhibit calcium influx and extracellular signal-regulated kinase (ERK) signaling via LPS receptors and/or as yet unidentified bikunin signaling receptors. By signaling via the LPS receptor, LPS increases calcium influx and yields phosphorylated ERK, which activates multiple transcription factors, such as nuclear factor kappaB (NF-kappaB) or early growth response-1 (Egr-1), which in turn promote cytokine expression. Deficits in the signaling cascades caused by free or cell-bound bikunin are predicted to down-regulate cytokine expression, render macrophages/neutrophils more inactive, and impair inflammatory processes. This brief review largely focuses on our current understanding of the apparent functions of bikunin, its ligands, the effector molecules with which it interacts, and its regulation.
Ultrasound-mediated oncolytic virus delivery and uptake for increased therapeutic efficacy: state of art (2015)

The field of ultrasound (US) has changed significantly from medical imaging and diagnosis to treatment strategies. US contrast agents or microbubbles (MB) are currently being used as potential carriers for chemodrugs, small molecules, nucleic acids, small interfering ribonucleic acid, proteins, adenoviruses, and oncolytic viruses. Oncolytic viruses can selectively replicate within and destroy a cancer cell, thus making them a powerful therapeutic in treating late-stage or metastatic cancer. These viruses have been shown to have robust activity in clinical trials when injected directly into tumor nodules. However limitations in oncolytic virus' effectiveness and its delivery approach have warranted exploration of ultrasound-mediated delivery. Gene therapy bearing adenoviruses or oncolytic viruses can be coupled with MBs and injected intravenously. Following application of US energy to the target region, the MBs cavitate, and the resulting shock wave enhances drug, gene, or adenovirus uptake. Though the underlying mechanism is yet to be fully understood, there is evidence to suggest that mechanical pore formation of cellular membranes allows for the temporary uptake of drugs. This delivery method circumvents the limitations due to stimulation of the immune system that prevented intravenous administration of viruses. This review provides insight into this intriguing new frontier on the delivery of oncolytic viruses to tumor sites.
Glutamate agonist activity (1995)

Antagonist action at dopamine D2 receptors appears to explain many, but not all of the effects of antipsychotic drugs. Because of the interactions of dopamine with glutamate, and the implication of the latter in the etiology of schizophrenia, possible effects of antipsychotic drugs on glutamate receptors were assessed in the present experiments. These studies showed that, at clinically relevant concentrations, the conventional neuroleptic haloperidol and the atypical antipsychotic clozapine had potent augmenting influences on the NMDA receptor. These data suggest that unique action at glutamate receptors may contribute to antipsychotic efficacy and emphasize the potential importance of glutamatergic dysfunction in the etiology of schizophrenia.
Vascular Endothelial Growth Factor (VEGF) Expression in Prostate Cancer and Benign Prostatic Hyperplasia (1997)

Widespread distribution of VEGF in prostate cancers and BPH specimens suggest that the VEGF165, VEGF189 isoforms and novel 90 and 110 kD forms detected may contribute to the establishment or progression of these conditions.
Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation (2001)

The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology of chronic inflammation, heart disease, stroke, the debilitating effects of diabetes mellitus, and the side effects of cancer therapy, not to mention embryonic development, innate and acquired immunity, is profound. Cardiovascular disease and diabetes alone represent the most significant health care problems in the developed world. Thus it is not surprising that understanding these pathways has attracted wide interest, and in the past 10 years, dramatic progress has been made. Accordingly, it is now becoming possible to envisage the transition of these findings to the development of novel treatment strategies. This review focuses on the biochemical components and regulation of mammalian stress-regulated mitogen-activated protein kinase (MAPK) pathways. The nuclear factor-kappa B pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260).
Fuzzy Information Retrieval Based on a Fuzzy Pseudothesaurus (1986)

A fuzzy bibliographic information retrieval based on a fuzzy thesaurus or on a fuzzy pseudothesaurus is described. A fuzzy thesaurus consists of two fuzzy relations defined on a set of keywords for the bibliography. The fuzzy relations are generated based on a fuzzy set model, which describes association of a keyword to its concepts. If the set of concepts in the fuzzy set model is replaced by the set of documents, the fuzzy relations are called a pseudothesaurus, which is automatically generated by using occurrence frequencies of the keywords in the set of documents. The fuzzy retrieval uses two fuzzy relations in addition, that is, a fuzzy indexing and a fuzzy inverted file: the latter is the inverse relation of the former. They are, however, related to different algorithms for indexing and retrieval, respectively. An algorithm of ordering retrieved documents according to the values of the fuzzy thesaurus is proposed. This method of the ordering is optimal in the sense that one can obtain documents of maximum relevance in a fixed time interval. An example of the fuzzy retrieval is shown on a prototype database. This method shows one of the simplest way to realize fuzzy retrieval in practical database systems.
Optimum Design of Microchannel Heat Sinks (1996)

Abstract Analyses have been performed to obtain momentum and thermal characteristics in microchannel heat sinks. The applicability of existing correlations for friction factor and Nusselt number is investigated. The study revealed that existing correlations based on the analytical results can predict the heat sink performance to within the accuracy limits acceptable for use in design. A user friendly computer code has been developed as an aid in the optimum design of microchannel heat sinks. The program, using thermal resistance models, operates in two modes. In mode one, the performance capabilities, power requirements and efficiencies of an existing heat sink design are evaluated. Mode two is used as a design tool for heat sink optimization. In this mode, given the overall heat sink geometry, fluid and substrate properties, and inlet and outlet boundary conditions, the program determines the optimum channel spacing and fin thickness. Implementation of the optimization scheme is presented and its effectiveness is evaluated. Improvements of up to 45% in heat transfer rates are observed by analyzing thermal resistance surface plots for wide ranges of fin thickness and channel spacing. In addition, the idea of designing heat sinks for turbulent conditions rather than laminar are examined. The results show that significant reductions in the total thermal resistance are not achieved by designing for turbulent flow. In contrast, significantly higher pumping power requirements are realized when designing for turbulent flow with only slight improvement in overall thermal performance.
An Alkyl Hydroperoxide Reductase from Salmonella typhimurium Involved in the Defense of DNA against Oxidative Damage (1989)

A peroxide reductase (peroxidase) which converts lipid hydroperoxides and other alkyl hydroperoxides to the corresponding alcohols, using either NADH or NADPH as the reducing agent, has been identified in both Salmonella typhimurium and Escherichia coli. This enzyme is shown to play a role in protecting against alkyl hydroperoxide mutagenesis. To our knowledge this work represents the first description of an NAD(P)H peroxidase in enteric bacteria and the first reported bacterial peroxidase to exhibit high activity toward alkyl hydroperoxides. A high performance liquid chromatography-based assay for the alkyl hydroperoxide reductase has been developed by monitoring the reduction of cumene hydroperoxide, a model alkyl hydroperoxide. By using this assay, the enzyme has been purified from a S. typhimurium regulatory mutant, oxyR1, which overexpresses a number of proteins involved in defenses against oxidative damage, and which contains 20-fold more of the alkyl hydroperoxide reductase than the wild-type strain. The purified activity requires the presence of two separable components having subunit molecular weights of 22,000 and 57,000. The 57-kDa protein contains a bound FAD cofactor and can use either NADH or NADPH as an electron donor for the direct reduction of redox dyes, or of alkyl hydroperoxides when combined with the 22-kDa protein. This enzyme may thus serve as a prokaryotic equivalent to the glutathione reductase/glutathione peroxidase system in eukaryotes.