Miracle-dz/UniFAR-FTUs huggingface dataset:
The RAG-HMG1 Complex Enforces the 12/23 Rule of V(D)J Recombination Specifically at the Double-Hairpin Formation Step

ABSTRACT A central unanswered question concerning the initial phases of V(D)J recombination has been at which step the 12/23 rule applies. This rule, which governs which variable (V), diversity (D), and joining (J) segments are able to pair during recombination, could operate at the level of signal sequence synapsis after RAG-HMG1 complex binding, signal nicking, or signal hairpin formation. It has also been unclear whether additional proteins are required to achieve adherence to the 12/23 rule. We developed a novel system for the detailed biochemical analysis of the 12/23 rule by using an oligonucleotide-based substrate that can include two signals. Under physiologic conditions, we found that the complex of RAG1, RAG2, and HMG1 can successfully recapitulate the 12/23 rule with the same specificity as that seen intracellularly and in crude extracts. The cleavage complex can bind and nick 12×12 and 23×23 substrates as well as 12×23 substrates. However, hairpin formation occurs at both of the signals only on 12×23 substrates. Moreover, under physiologic conditions, the presence of a partner 23-bp spacer suppresses single-site hairpin formation at a 12-bp spacer and vice versa. Hence, this study illustrates that synapsis suppresses single-site reactions, thereby explaining the high physiologic ratio of paired versus unpaired V(D)J recombination events in lymphoid cells.
Prognostic value of E-cadherin, beta-catenin, CD44v6, and HER2/neu in metastatic cutaneous adenocarcinoma.

CONTEXT Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases. OBJECTIVE To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade. DESIGN E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%). RESULTS Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin--a member of the cadherin family functioning as an invasion suppressor molecule. CONCLUSIONS These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.
Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial.

CONTEXT Postherpetic neuralgia (PHN) is a syndrome of often intractable neuropathic pain following herpes zoster (shingles) that eludes effective treatment in many patients. OBJECTIVE To determine the efficacy and safety of the anticonvulsant drug gabapentin in reducing PHN pain. DESIGN Multicenter, randomized, double-blind, placebo-controlled, parallel design, 8-week trial conducted from August 1996 through July 1997. SETTING Sixteen US outpatient clinical centers. PARTICIPANTS A total of 229 subjects were randomized. INTERVENTION A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo. Treatment was maintained for another 4 weeks at the maximum tolerated dose. Concomitant tricyclic antidepressants and/or narcotics were continued if therapy was stabilized prior to study entry and remained constant throughout the study. MAIN OUTCOME MEASURES The primary efficacy measure was change in the average daily pain score based on an 11-point Likert scale (0, no pain; 10, worst possible pain) from baseline week to the final week of therapy. Secondary measures included average daily sleep scores, Short-Form McGill Pain Questionnaire (SF-MPQ), Subject Global Impression of Change and investigator-rated Clinical Global Impression of Change, Short Form-36 (SF-36) Quality of Life Questionnaire, and Profile of Mood States (POMS). Safety measures included the frequency and severity of adverse events. RESULTS One hundred thirteen patients received gabapentin, and 89 (78.8%) completed the study; 116 received placebo, and 95 (81.9%) completed the study. By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001). Secondary measures of pain as well as changes in pain and sleep interference showed improvement with gabapentin (P<.001). Many measures within the SF-36 and POMS also significantly favored gabapentin (P< or =.01). Somnolence, dizziness, ataxia, peripheral edema, and infection were all more frequent in the gabapentin group, but withdrawals were comparable in the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in the placebo group). CONCLUSIONS Gabapentin is effective in the treatment of pain and sleep interference associated with PHN. Mood and quality of life also improve with gabapentin therapy.
Stabilization analysis for a class of multiple interval time-varying delays system

The delay-dependent stability problem for a class of multiple interval time-varying delays system is investigated in this paper, in which the derivatives of the time-varying delays are unknown. Delay-dependent stability criterions have been formulated in LMI forms based on integral equality approach. Some advantages are showed in this paper: (1) the results are free from the restrictions on the derivatives of the time-varying delays and can be applied to fast interval time-varying delays systems (2) integral equality approach reduces the conservatism of the system (3) the results are more general. Finally, a numeric example proves that the method is effective and superior.
Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia.

Release of urokinase plasminogen activator receptor during urosepsis and endotoxemia. Background The urokinase receptor (uPAR; CD87) is a multifunctional molecule involved in fibrinolysis, in proteolysis, in renal tubular functions, and in migration and adhesion of inflammatory cells to the site of infection. Methods To gain insight into systemic and local release of uPAR and into its regulation during urosepsis, which is one of the leading causes of chronic renal failure, uPAR was measured in urine and plasma of healthy human controls ( N = 20), patients with culture-proven urosepsis ( N = 30), and healthy human volunteers intravenously injected with endotoxin ( N = 7). Results Patients had elevated uPAR levels in both plasma and urine. Three hours after endotoxin challenge in volunteers, there was also a significant increase of uPAR in plasma and in urine. The urine/plasma ratio for uPAR was highly elevated during urosepsis and experimental endotoxemia, suggesting local production in the kidney. Accordingly, damaged tubuli strongly expressed uPAR during pyelonephritis. Moreover, tubular epithelial cells produced uPAR in vitro, and this secretion was strongly up-regulated after stimulation with interleukin-1β or tumor necrosis factor-α. Conclusions We found that uPAR is released systemically and in the urinary tract during urosepsis and experimental endotoxemia. This systemic and renal production of uPAR during pyelonephritis may play a central role in eliminating the infection and protecting renal function.
Pro-active call center treatment support (PACCTS) to improve glucose control in type 2 diabetes: a randomized controlled trial.

OBJECTIVE To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS A randomized controlled implementation trial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA(1c) level. The primary outcome was absolute reduction in HbA(1c), and the secondary outcome was the proportion of patients reducing HbA(1c) by at least 1%. RESULTS A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA(1c) values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA(1c) improved by 0.31% (95% CI 0.11-0.52, P = 0.003) overall in the PACCTS patients. For patients with baseline HbA(1c) >7%, the improvement increased to 0.49% (0.21-0.77, P < 0.001), whereas in patients with baseline HbA(1c) <7% there was no change. The difference in the proportions of patients achieving a >/=1% reduction in HbA(1c) significantly favored the PACCTS intervention: 10% (4-16, P < 0.001) overall and 15% (7-24, P < 0.001) for patients with baseline HbA(1c) >7%. CONCLUSIONS In an urban Caucasian trial population with blood glucose HbA(1c) >7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control.
Glaucoma and disability: which tasks are affected, and at what stage of disease?

Purpose of review To summarize recent work from clinical and epidemiological studies that describe how, and at what stage, glaucoma affects the performance of important vision-related activities. Recent findings Difficulties with the extremes of lighting are the most frequent complaint in glaucoma. Individuals with bilateral glaucoma also self-report difficulty with a broad array of tasks, including reading, walking, and driving. Bilateral glaucoma is associated with driving cessation and limitation, bumping into objects, slower walking, and falls. Some, but not all, studies also demonstrate higher accident rates in glaucoma. Measurable effects on reading speed have only been observed with field damage severe enough to affect binocular central acuity. Summary Glaucoma with bilateral visual field loss is associated with increased symptoms and a measurable decline in mobility and driving. Further work is necessary to establish whether unilateral glaucoma has a significant impact on patients, to determine whether reading difficulty is common in patients with bilateral glaucoma, and to establish the effects of lighting conditions on task performance in glaucoma.
Decoding For Iterative Reed-solomon Coding Schemes

For high density data storage systems channel errors may appear in the form of bursts. This error correlation can significantly degrade the bit error rate on the subsequent stages of data processing. To correct error bursts the interleaved Read-Solomon (RS) codes are used. Usually, after the deinterleaving, the received words are decoded one by one by the same error correction algorithm. In this paper, a novel approach for the decoding of interleaved codes is proposed. It is based on a notion of covering error locators that locate error positions in two or more adjacent words. To compute the covering error locator polynomial, a modification of the Berlekamp-Massey algorithm is proposed. It is shown that with a certain probability of failure the proposed algorithm can correct more errors than the designed error correction ability. The algorithm may also be useful in a more general case of interleaved coding schemes with both rows and columns encoded by RS code.
Effects of Monitoring the Usage of Antibiotics: An Interhospital Comparison

Use of selected systemic antimicrobial agents at Boston City Hospital (BCH) has been monitored by requiring that choice of those agents be justified to a member of the Infectious Diseases Unit before the agent is dispensed for use in a patient. The amounts of various antimicrobial agents and classes of agents used at BCH in 1972 differed considerably from amounts used in other hospitals where restraint was not employed. Whether these differences in usage led to better care for the patient could not be determined from the data presented. These aspects must be studied in greater detail to determine the benefits, if any, that may be derived from such surveillance and control, especially in view of recent proposals for implementation of “peer review” in this as well as other areas.
Experimental setup for the extraction of power amplifier dynamic volterra model and design of digital baseband predistorter

This paper deals with the two-memory path nonlinear integral model introduced previously which has shown that it accurately reproduces the nonlinear memory effects in Radio Frequency Amplifiers. Due to the relative complexity of the required measurement setup, the model presented has thus far been extracted and validated upon circuit simulations only. Here, we present a relatively simple and effective experimental setup procedure to identify the PA model. Furthermore, using the same setup we have been able to extract both the PA model and its inverse characteristic, leading directly to the design of a digital linearizer able to compensate effectively for the nonlinear memory effects. The linearizer has shown the capability to reduce significantly the spectral regrowth for different kinds of signals that differ fundamentally from the extraction stimulus. Experimental results carried out on a 10 dB gain GaAs power amplifier are presented for both the power amplifier and predistorter identification.
Preovulatory Overripeness of the Egg in the Human Subject

Anomalies of conception which endanger the ensuing pregnancy have been reviewed. The range of possible consequences include “occult” and early spontaneous abortions, a wide spectrum of chromosome defects, developmental anomalies, such as those of the brain (with a wide range of neuro‐psychopathology as a consequence) and possibly some other abnormalities of gestation. Pathology either of the pregnancy or of the products of conceptions caused by preovulatory overripeness ovopathy may be expected from conceptions that occur at times of changing endocrine patterns, reflected clinically in a transition from anovulation and vice versa. One can anticipate finding this conceptopathology reflected epidemiologically in a U‐shaped curve in relation to the reproductive age of the mother, in another U‐shaped curve relevant to the duration of the conception interval, and finally in a 4‐peaked birth curve related to seasonal variations of the ovulatory patterns.
The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland.

BACKGROUND XRCC2 and XRCC3 genes are structurally and functionally related to RAD51 which plays an important role in homologous recombination, the process frequently involved in cancer transformation. MATERIAL AND METHODS In the present work the distribution of genotypes and frequency of alleles of the RAD51 G135C polymorphism, XRCC2 Arg 188His and XRCC3 Thr241Met polymorphism in 790 cases of breast cancer were investigated. The control group consisted of 798 cancer-free blood donors (age +/- 5 years) who were sex and ethnicity-matched. The polymorphisms were determined by PCR-RFLP methods. We also correlated genotypes with the clinical characteristics of breast cancer patients. RESULTS Our results obtained for the 135G>C polymorphism of the RAD51 gene indicated that both the C/C genotype and the C allele are strongly associated with breast cancer. The Arg/His genotype of XRCC2 (OR = 2.16, 95% CI = 1.48-3.16) and Thr/Met of XRCC3 increased the risk of type I breast cancer occurrence (OR = 2.33, 95% CI = 1.60-3.41). We did not find any association with the RAD51, XRCC2/3 gene polymorphism and estrogen and progesterone receptor status. CONCLUSION The results support the hypothesis that the polymorphism of RAD51 and XRCC2/3 gene may be associated with the incidence of sporadic breast cancer in Polish women.
Chemically resistant encapsulation for MEMS release

Serguei Stoukatch, Microsys, Universite de Liege; Liege, Belgium Ester Tooten, ICTEAM, Universite Catholique de Louvain; Louvain-La-Neuve, Belgium Fabrice Axisa, Microsys, Universite de Liege; Liege, Belgium Bruno Heusdens, TAIPRO Engineering, Seraing, Belgium Laurent A. Francis, ICTEAM, Universite Catholique de Louvain; Louvain-La-Neuve, Belgium Jacques Destine, EMMI, Universite de Liege; Liege, Belgium
FASTRUN: A special purpose, hardwired computer for molecular simulation

We describe the design, construction, and performance of a special purpose, hardwired accelerator for molecular mechanical calculations called FASTRUN. The processor was designed at Columbia University in 1984, constructed in the Instrumentation Division of Brookhaven National Laboratory, and delivered to Columbia in final form in 1989. It was rendered functional for molecular mechanics in early 1990. Together with its host Star array processor, FASTRUN has a measured performance for molecular dynamics simulations which compares favorably with present day supercomputers. The hardware replication cost of FASTRUN is on the order of $100,000.00
A 0.13µm CMOS 0.1–20MHz bandwidth 86–70dB DR multi-mode DT ΔΣ ADC for IMT-Advanced

This paper presents a reconfigurable tri-level/multi-bit multi-mode ΔΣ modulator implemented in 0.13 µm CMOS. The modulator covers between 0.1 MHz and 20 MHz signal bandwidth which makes it suitable for cellular applications including 4G radio systems, also known as IMT-Advanced. With a maximum sampling rate of 400MHz, the modulator achieves between 86dB and 70dB DR for 100kHz and 20MHz signal bandwidth, respectively, at a scalable power consumption between 2 mW and 34 mW from a 1.2 V supply, including the reference buffer.
Implementation of an Efficient SRAM for Ultra-Low Voltage Application Based on ST for Better Read Stability and Write Ability

Operation of standard 6T static random access memory (SRAM) cells at sub or near threshold voltages is unfeasible, predominantly due to degraded static noise margins (SNM) and poor robustness. We analyze Schmitt-Trigger (ST)-based differential-sensing static random access memory (SRAM) bitcells for ultralow-voltage operation. The ST-based SRAM bitcells address the fundamental conflicting design requirement of the read versus write operation of a conventional 6T bitcell. The ST operation gives better read- stability as well as better write-ability compared to the standard 6T bitcell. In this paper we are going to propose a new SRAM bitcell for the purpose of read stability and write ability by using 90nm technology , and less power consumption, less area than the existing Schmitt trigger1 based SRAM. Design and simulations were done using DSCH and Microwind. Index Terms: read stability, write ability, Schmitt trigger. I. Introduction PORTABLE electronic devices have extremely low power requirement to maximize the battery lifetime. Various device-/circuit-architectural-level techniques have been implemented to minimize the power consumption. Supply voltage scaling has significant impact on the overall power dissipation.With the supply voltage reduction, the dynamic power reduces quadratically while the leakage power reduces linearly (to the first order). However, as the supply voltage is reduced, the sensitivity of circuit parameters to process variations increases. This limits the circuit operation in the low-voltage regime, particularly for SRAM bitcells employing Minimum-sizedtransistor. These minimum geometry transistors are vulnerable to interdie as well as intradie process variations. Intradie process variations include random dopant fluctuation (RDF) and line edge roughness (LER). This may result in the threshold voltage mismatch between the adjacent transistors in a memory bitcell, resulting in asymmetrical characteristics. The combined effect of the lower supply voltage along with the increased process variations may lead to and increased memory failures such as read-failure, hold-failure, write- failure, access-time failure. Moreover, it is predicted that embedded cache memories, which are expected to occupy a significant portion of the total die area, will be more prone to failures with scaling.
Native state dynamics and mechanical properties of human topoisomerase I within a structure‐based coarse‐grained model

A coarse grained molecular dynamics model with an implicit solvent is used to elucidate properties of the human topoisomerase I. The model is defined through the native structure and it allows covering significantly longer time scales than in all atom simulations. Single residue and double residue motional characteristics are studied. The results are consistent with all atom simulations reported in the literature indicating usefulness of the model in further studies of this protein. Novel findings include broadening of the description of the dynamic behavior of the lip and hinge regions and a characterization of the motional properties of the RRM binding site of the enzyme. We also consider mechanical stretching of the protein and identify sources of the force peaks. The elastic properties of topoisomerase I are predicted to be average in comparison to other proteins, yielding a maximum force of resistance to pulling which should be of order 120 pN. The contact unraveling pattern is consistent with the understanding of the structure and function of the protein. We find supporting evidence for the hypothesis that the C‐terminal domain acquires an ordered structure upon binding with the core enzyme even though it forms a molten globule when in isolation. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Content Centric Routing for Future Generation Networks

In this poster, we propose a content centric protocol for the filtering and the distribution of data between users. This protocol has the advantage of working either in current IP networks or new networking frameworks like the ANA framework. Our protocol consists of a distributed filtering process associated to a dynamic optimization process that selects the best content matching a client request at a given time. The performance evaluation of the protocol presented a satisfactory behavior in IP networks, while the implementation done using the ANA prototype allowed to adapt our protocol to a new autonomic framework that we hope, will be one of the leading autonomic framework of the future generation networks. However, we have a lot of work to do. We are working on a Java prototype to be deployed in platforms like Planetlab and Onelab in order to test its performance in a large-scale IP infrastructures. We are also working on the deployment of the implemented prototype in an ANA testbed and the execution some scenarios that could help us to prove its autonomic features.