gebhart/patrepeval huggingface dataset:
Public-key cryptosystems from the worst-case shortest vector problem (2009)

We construct public-key cryptosystems that are secure assuming theworst-case hardness of approximating the minimum distance on n-dimensional lattices to within small Poly(n) factors. Prior cryptosystems with worst-case connections were based either on the shortest vector problem for a special class of lattices (Ajtai and Dwork, STOC 1997; Regev, J. ACM 2004), or on the conjectured hardness of lattice problems for quantum algorithms (Regev, STOC 2005). Our main technical innovation is a reduction from variants of the shortest vector problem to corresponding versions of the "learning with errors" (LWE) problem; previously, only a quantum reduction of this kind was known. As an additional contribution, we construct a natural chosen ciphertext-secure cryptosystem having a much simpler description and tighter underlying worst-case approximation factor than prior schemes.
Immunological approaches for the treatment of prostate cancer. (1998)

Conventional therapies for patients with early-stage relapsed prostate cancer often do not provide an acceptable quality of life. These patients often have increasing PSAs as the sole manifestation of their disease recurrence and represent a unique subgroup of patients for whom alternative treatment strategies are needed. The patients are asymptomatic and may be an appropriate population for targeted immunological approaches. Vaccine therapies, based on synthetically constructed, naturally occurring prostate-associated antigens or genetically modified immune cells, offer exciting new approaches toward treating this disease with resulting antitumor effects and minimal toxicities. The results of clinical trials using these technologies reinforces the use of immunological approaches for the treatment of prostate cancer.
Rational design of an animal model for alzheimer's disease: introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent (1996)

A major obstacle to understanding the pathogenesis of Alzheimer's disease is the lack of easily studied animal models. Our approach is to apply transgenic methods to humanize mice and rats, employing methods that introduce large genomic transgenes, because this improves the level of transgene protein expression and the tissue specificity of expression. Our plan is to reproduce AD pathology in rodents by making them transgenic for several human proteins involved in AD. This report describes transgenic animal lines that we have produced, and summarizes our current approach and future plans. Two human genes known to be involved in AD pathology are the amyloid precursor protein (APP) and the E4 isoform of apolipoprotein E (apoE4). So far, we have produced and analyzed a transgenic line carrying the entire human APP gene cloned in a yeast artificial chromosome. We have also produced but not yet analyzed a mouse carrying the human apoE4 gene. Work is in progress to produce a transgenic line carrying a disease-causing mutation in the human APP gene. As we produce these animals, we are breeding them together, and also breeding them with a mouse line that lacks endogenous apoE, to produce an animal model carrying several human proteins whose interaction is believed to be instrumental in development of AD pathology. These transgenic animals will be useful for dissecting the biochemical and physiological steps leading to AD, and for development of therapies for disease intervention.
A mask-to-wafer alignment and gap setting method for x-ray lithography using gratings (1991)

A new optical-heterodyne interferometry alignment and gap setting method for x-ray lithography is developed, where the phases of beat signals are used for detection. The fact that the lateral displacement and the gap between mask and wafer can be detected independently is shown, based on the results of analysis and experiments. Two pairs of gratings are arranged as detection marks. One pair forms a window on the mask and a checkerboard grating on the wafer, while another pair forms two linear gratings at right angles to each other. Two He-Ne laser beams with slightly different frequencies illuminate the gratings from the ±1st-order diffraction light directions. The lateral displacement is detected by measuring the beat signal phase difference between the two (0,1)th-order diffraction lights from two pairs of gratings. To detect the gap, the signal phase difference between the (0,1)th- and (1,1)th-order diffraction lights from the pair of linear gratings is used. Better than 0.02 μm (3σ) alignment repeatability and 0.1 μm gap setting accuracy have been achieved.
Evaluation of murine norovirus as a surrogate for human norovirus and hepatitis A virus in heat inactivation studies (2009)

Caution should be used when extrapolating surrogate virus data for HuNoV. Although not conclusive, our results suggest that HuNoV may be more resistant to heat than either HAV or MNV.
Proteomic Identification of Protease Cleavage Sites Characterizes Prime and Non-prime Specificity of Cysteine Cathepsins B, L, and S (2011)

Cysteine cathepsins mediate proteome homeostasis and have pivotal functions in diseases such as cancer. To better understand substrate recognition by cathepsins B, L, and S, we applied proteomic identification of protease cleavage sites (PICS) for simultaneous profiling of prime and non-prime specificity. PICS profiling of cathepsin B endopeptidase specificity highlights strong selectivity for glycine in P3' due to an occluding loop blocking access to the primed subsites. In P1', cathepsin B has a partial preference for phenylalanine, which is not found for cathepsins L and S. Occurrence of P1' phenylalanine often coincides with aromatic residues in P2. For cathepsin L, PICS identifies 845 cleavage sites, representing the most comprehensive PICS profile to date. Cathepsin L specificity is dominated by the canonical preference for aromatic residues in P2 with limited contribution of prime-site selectivity determinants. Profiling of cathepsins B and L with a shorter incubation time (4 h instead of 16 h) did not reveal time-dependency of individual specificity determinants. Cathepsin S specificity was profiled at pH 6.0 and 7.5. The PICS profiles at both pH values display a high degree of similarity. Cathepsin S specificity is primarily guided by aliphatic residues in P2 with limited importance of prime-site residues.
Future prospects for vaccine adjuvants. (1988)

Since the landmark experiments of Ramon 60 years ago, attempts have been made to augment the humoral and cellular responses to administered antigens in order to develop more potent and less toxic vaccines. The need for an acceptable adjuvant suitable for clinical use has been underscored by recent advances in recombinant biotechnology and synthetic chemistry which have made it possible to create antigens that are smaller and better characterized, yet less immunogenic, than before. It is likely that these antigens will require an adjuvant to achieve protective immunity. Some of these same technological advances, together with a better understanding of the immune system in general, have permitted the study of adjuvants to evolve from an empirical field to a developmental one. This article discusses the currently known agents capable of immunopotentiation and possible strategies for their use in future vaccines.
Glucocorticoid-Induced Osteoporosis: Why Kids Are Different (2020)

Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian <b>ST</b>eroid-associated <b>O</b>steoporosis in the <b>P</b>ediatric <b>P</b>opulation ("<b>STOPP</b>") Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.
[Protection from gastroduodenal adverse effects of acetylsalicylic acid with ranitidine. An endoscopic controlled double-blind study of healthy subjects]. (1991)

Ranitidine protects against gastroduodenal mucosal damage associated with low-dose ASA therapy/Endoscopically evaluated double-blind study in healthy volunteers In a randomized double-blind crossover study the gastroduodenal tolerability of 300 mg ASA mane (8 a.m.) has been evaluated in the presence of 300 mg ranitidine nocte (8 p.m.) or placebo in 10 healthy volunteers using upper GI-endoscopy. The treatment periods lasted 14 d. Endoscopic controls were performed at entry, and repeated at day 7 and day 14. At entry the mean endoscopic score averaged 0.9 +/- 0.1 in the ASA/placebo-group and 0.8 +/- 0.1 in the ASA/ranitidine-group. 300 mg ASA mane induced in the placebo-experiments marked gastroduodenal ulcerations both at day 7 and day 14 (7.3 +/- 1.3 and 8.2 +/- 2.1, respectively). Concommittant administration of 300 mg ranitidine nocte afforded almost full protection against 300 mg ASA mane both on day 7 and day 14 (1.6 +/- 0.4 and 1.7 +/- 0.5, respectively) (p less than 0.05). These data suggest that nocturnal coadministration of ranitidine 300 mg reduces almost completely gastroduodenal lesions evoked by acetylsalicylic acid 300 mg mane.
Immunosuppressors as Multidrug Resistance Reversal Agents (2009)

Multidrug-resistance (MDR) is the major reason for failure of cancer therapy. ATP-binding cassette (ABC) transporters contribute to drug resistance via ATP-dependent drug efflux. P-glycoprotein (Pgp), which is encoded by MDR1 gene, confers resistance to certain anticancer agents. The development of agents able to modulate MDR mediated by Pgp and other ABC transporters remained a major goal for the past 20 years. The calcium blocker verapamil was the first drug shown to be a modulator of Pgp, and since many different chemical compounds have been shown to exert the same effect in vitro by blocking Pgp activity. These included particularly immunosuppressors. Cyclosporin A (CSA) was the first immunosuppressor that have been shown to modulate Pgp activity in laboratory models and entered very early into clinical trials for reversal of MDR. The proof of reversing activity of CSA was found in phase II studies with myeloma and acute leukemia. In phase III studies, the results were less convincing regarding the response rate, progression-free survival, and overall survival, which were detected in advanced refractory myeloma. The non-immunosuppressive derivative PSC833 (valspodar) was subsequently developed. This compound showed tenfold higher potency in reversal of MDR mediated by Pgp. However, pharmacokinetic interactions required reductions in the dose of the concurrently administered anticancer agents. The pharmacokinetic interactions were likely because of decreased clearance of the anticancer agents, possibly as a result of Pgp inhibition in organs such as the gastrointestinal tract and kidney, as well as inhibition of cytochrome P450. Finally, CSA and PSC833 have been shown also to modulate the ceramide metabolism which stands as second messenger of anticancer agent-induced apoptosis. In fact, CSA and PSC833 are also able to respectively inhibit ceramide glycosylation and stimulate de novo ceramide synthesis. This could enhance the cellular level of ceramide and potentiate apoptosis induced by some anticancer agents.
Near-Ohmic Contact of n-GaAs with GaS/GaAs Quasi-Metal-Insulator-Semiconductor Structure (1998)

We report on the current-voltage ( I – V ) characteristics of a metal/ultrathin GaS (thickness&lt;100 Å)/n + -GaAs (carrier concentration=2×10 18 cm -3 ) quasi-metal-insulator-semiconductor (QMIS) structure. The GaS was grown by molecular beam epitaxy (MBE) employing the precursor tertiarybutyl-galliumsulfide-cubane ([(t-Bu)GaS] 4 ). The I – V characteristics of the QMIS structure depend on the work function of various metals (Au, Al, Ti). We discovered that a QMIS structure leads to a reduction of Schottky-barrier height itself. Furthermore, we demonstrated near-ohmic contact (contact resistivity=3.7×10 -3 Ωcm 2 ) for a Ti/97-Å-thick GaS/n + -GaAs QMIS structure. From the relationship between the semiconductor barrier height and the metal work function, we determined that Fermi level pinning was almost eliminated by GaS passivation.
A natural variant of bovine dopamine β‐monooxygenase with phenylalanine as residue 208: purification and characterization of the variant homo‐ and heterotetramers of (F208)4 and (F208)2(L208)2 (1996)

Bovine dopamine beta-monooxygenase was purified from each of 18 individual adrenal glands by the method we have developed for the rapid purification of the enzyme from a single adrenal gland. Differential peptide mapping of the 18 enzyme preparations following fluorescence labeling of their cysteine residues revealed the presence of a novel variant with Phe as residue 208 in 14 adrenal glands; seven of them were homozygous for the variant allele and the remaining seven heterozygous. The variant enzyme was a tetramer and exhibited kinetic and structural properties similar to those of the wild-type tetramer (L208)4. These results indicate an allelic polymorphism and codominant expression of the two alleles of the enzyme gene.
Lipopolysaccharide-Induced Apoptosis of Endothelial Cells and Its Inhibition by Vascular Endothelial Growth Factor (2002)

Endothelial injury is a major manifestation of septic shock induced by LPS. Recently, LPS was shown to induce apoptosis in different types of endothelial cells. In this study, we observed that pretreatment with vascular endothelial growth factor (VEGF), a known cell survival factor, blocked LPS-induced apoptosis in endothelial cells. We then further defined this LPS-induced apoptotic pathway and its inhibition by VEGF. We found that LPS treatment increased caspase-3 and caspase-1 activities and induced the cleavage of focal adhesion kinase. LPS also augmented expression of the pro-apoptotic protein Bax and the tumor suppressor gene p53. The pro-apoptotic Bax was found to translocate to the mitochondria from the cytosol following stimulation with LPS. Pretreatment of endothelial cells with VEGF inhibited the induction of both Bax and p53 as well as the activation of caspase-3. These data suggest that VEGF inhibits LPS-induced endothelial apoptosis by blocking pathways that lead to caspase activation.
Sequence and characterization of mxaB, a response regulator involved in regulation of methanol oxidation, and of mxaW, a methanol-regulated gene in Methylobacterium extorquens AM1 (1998)

In the facultative serine cycle methylotroph Methylobacterium extorquens AM1, mxaB is required for regulation of methanol oxidation and is located at the end of a large cluster of methylotrophy genes that begins with mxaF. The sequence of mxaB has been obtained and indicates that the gene product is a member of the response regulator family. None of the open reading frames near mxaB showed sequence identity to sensor kinases. Complementation studies suggest a promoter may be located adjacent to mxaB. Another gene (mxaW) is present immediately upstream of mxaF, divergently transcribed from a methanol-inducible promoter. The sequence in the region of mxaW was also obtained. MxaW showed no identity to known proteins. Mutations in mxaW and in an adjacent open reading frame, OrfR, had no effect on growth of M. extorquens AM1 on methanol or other substrates. The MxaW mutant had normal methanol dehydrogenase activity and normal transcription of the mxaF promoter. Therefore, the function of mxaW is unknown.
CELLULAR REQUIREMENTS FOR THE PRIMARY IN VITRO ANTIBODY RESPONSE TO DNP-FICOLL (1974)

The cellular requirements for the primary in vitro IgM and IgG response to dinitrophenyl-substituted Ficoll were examined. Neither thymus-derived lymphocytes nor macrophage-rich splenic adherent cells were required for anti-DNP antibody synthesis. DNP-Ficoll is therefore tentatively classified as a "thymic-independent" antigen.
Genetic Diversity of Protease and Reverse Transcriptase Sequences in Non-Subtype-B Human Immunodeficiency Virus Type 1 Strains: Evidence of Many Minor Drug Resistance Mutations in Treatment-Naive Patients (2000)

Most human immunodeficiency virus (HIV) drug susceptibility studies have involved subtype B strains. Little information on the impact of viral diversity on natural susceptibility to antiretroviral drugs has been reported. However, the prevalence of non-subtype-B (non-B) HIV type 1 (HIV-1) strains continues to increase in industrialized countries, and antiretroviral treatments have recently become available in certain developing countries where non-B subtypes predominate. We sequenced the protease and reverse transcriptase (RT) genes of 142 HIV-1 isolates from antiretroviral-naive patients: 4 belonged to group O and 138 belonged to group M (9 subtype A, 13 subtype B, 2 subtype C, 5 subtype D, 2 subtype F1, 9 subtype F2, 4 subtype G, 5 subtype J, 2 subtype K, 3 subtype CRF01-AE, 67 subtype CRF02-AG, and 17 unclassified isolates). No major mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors were detected. Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I). In contrast, many accessory mutations were found, especially in the protease gene. Only 5.6% of the 142 strains, all belonging to subtype B or D, had no mutations in the protease gene. Sixty percent had one mutation, 22.5% had two mutations, 9.8% had three mutations, and 2.1% (all group O strains) had four mutations. In order of decreasing frequency, the following mutations were identified in the protease gene: M36I (86.6%), L10I/V (26%), L63P (12.6%), K20M/R (11.2%), V77I (5.6%), A71V (2.8%), L33F (0.7%), and M46I (0.7%). R211K, an accessory mutation associated with NRTI resistance, was also observed in 43.6% of the samples. Phenotypic and clinical studies are now required to determine whether multidrug-resistant viruses emerge more rapidly during antiretroviral therapy when minor resistance-conferring mutations are present before treatment initiation.
High frequency vector-mediated transformation and gene replacement in Tetrahymena (1994)

Recently, we developed a mass DNA-mediated transformation technique for the ciliated protozoan Tetrahymena thermophila that introduces transforming DNA by electroporation into conjugating cells. Other studies demonstrated that a neomycin resistance gene flanked by Tetrahymena H4-I gene regulatory sequences transformed Tetrahymena by homologous recombination within the H4-I locus when microinjected into the macronucleus. We describe the use of conjugant electrotransformation (CET) for gene replacement and for the development of new independently replicating vectors and a gene cassette that can be used as a selectable marker in gene knockout experiments. Using CET, the neomycin resistance gene flanked by H4-I sequences transformed Tetrahymena, resulting in the replacement of the H4-I gene or integrative recombination of the H4-I/neo/H4-I gene (but not vector sequences) in the 5' or 3' flanking region of the H4-I locus. Gene replacement was obtained with non-digested plasmid DNA but releasing the insert increased the frequency of replacement events about 6-fold. The efficiency of transformation by the H4-I/neo/H4-I selectable marker was unchanged when a single copy of the Tetrahymena rDNA replication origin was included on the transforming plasmid. However, the efficiency of transformation using CET increased greatly when a tandem repeat of the replication origin fragment was used. This high frequency of transformation enabled mapping of the region required for H4-I promoter function to within 333 bp upstream of the initiator ATG. Similarly approximately 300 bp of sequence downstream of the translation terminator TGA of the beta-tubulin 2 (BTU2) gene could substitute for the 3' region of the H4-I gene. This hybrid H4-I/neo/BTU2 gene did not transform Tetrahymena when subcloned on a plasmid lacking an origin of replication, but did transform at high frequency on a two origin plasmid. Thus, the H4-I/neo/BTU2 cassette is a selectable marker that can be used for gene knockout in Tetrahymena. As a first step toward constructing a vector suitable for cloning genes by complementation of mutations in Tetrahymena, we also demonstrated that the vector containing 2 origins and the H4-I/neo/BTU2 cassette can co-express a gene encoding a cycloheximide resistant ribosomal protein.